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Clinical Trial Results:
The H10 EORTC/GELA/IIL randomized Intergroup trial on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in patients with supradiaphragmatic stage I/II Hodgkin's lymphoma.

Summary
EudraCT number	2005-002765-37
Trial protocol	NL BE DK FR IT SK
Global end of trial date	09 Jan 2015

Results information
Results version number	v1(current)
This version publication date	10 Aug 2016
First version publication date	10 Aug 2016
Other versions
Summary report(s)	Trial design

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

20051

ISRCTN number

US NCT number

NCT00433433

WHO universal trial number (UTN)

Sponsor organisation name

European Organisation for Research and Treatment of Cancer

Sponsor organisation address

Avenue E. Mounier 83/11, Brussels, Belgium, 1200

Public contact

Project, Budget and Regulatory Dept, European Organisation for Research and Treatment of Cancer, +32 27441062, regulatory@eortc.be

Scientific contact

Project, Budget and Regulatory Dept, European Organisation for Research and Treatment of Cancer, +32 27441062, regulatory@eortc.be

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Jan 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

30 Jun 2014

Global end of trial reached?

Yes

Global end of trial date

09 Jan 2015

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to evaluate whether chemotherapy alone is as effective -but less toxic-, as combined modality treatment in terms of progression-free survival (PFS), in patients with stages I/II Hodgkin’s lymphoma who are FDG-PET scan negative after two cycles of ABVD. This question will be addressed in the group of patients with favorable stages I/II disease as well as in those with unfavorable stages I/II disease. A secondary objective is to evaluate whether early change of chemotherapy from ABVD to escalated BEACOPP improves the progression-free survival of patients who are FDG-PET-positive after two cycles of ABVD, as compared with those who continue on standard ABVD in both favorable as well as unfavorable subsets of patients.

Protection of trial subjects

The responsible investigator has ensured that this study has been conducted in agreement with either the Declaration of Helsinki (Tokyo, Venice, Hong Kong, Somerset West and Edinburgh amendments) and/or the laws and regulations of the country, whichever provides the greatest protection of the patient. The protocol has been written, and the study has been conducted according to the ICH Harmonized Tripartite Guideline on Good Clinical Practice (ICH-GCP). The protocol has been approved by the competent ethics committee(s) as required by the applicable national legislation.

Background therapy

All randomized patients (standard and experimental arms), in both trial subsets (Favorable and Unfavorable), will be administered two cycles of ABVD (Doxorubicin 25 mg/m2 i.v., Bleomycin 10 mg/m2 i.v./i.m., Vinblastine 6 mg/m2 i.v., Dacarbazine 375 mg/m2 i.v. at day 1 and 15 of each cycle) and will subsequently have a FDG-PET scan, together with a conventional restaging (chest X-ray and CT-thorax).

Evidence for comparator

Standard treatment for patients with early stage Hodgkin lymphoma, with favorable or unfavorable prognosis, consists of chemotherapy (mainly ABVD) followed by radiotherapy. Fermé C, Eghbali H, Meerwaldt JH, et al: Chemotherapy plus involved-field radiation in early stage Hodgkin’s disease. N Engl J Med 357:1916-1927, 2007 Engert A, Plutschow A, Eich HT, et al: Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363:640-652, 2010

Actual start date of recruitment

23 Nov 2006

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy, Scientific research

Long term follow-up duration

20 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 332

Country: Number of subjects enrolled

Slovakia: 15

Country: Number of subjects enrolled

Belgium: 162

Country: Number of subjects enrolled

Denmark: 31

Country: Number of subjects enrolled

France: 970

Country: Number of subjects enrolled

Italy: 407

Country: Number of subjects enrolled

Croatia: 20

Country: Number of subjects enrolled

Switzerland: 13

Worldwide total number of subjects

1950

EEA total number of subjects

1937

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1843

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 1950 patients were randomized between 23rd November 2006 and 22nd June 2011 in 158 institutions from 8 countries. Two additional patients were randomized but no informed consent was found (patients 62, 1192); these two patients are thus not reported.

Screening details

Histologically confirmed Hodgkin's lymphoma (HL), except for nodular, lymphocyte predominant subtype (nodular paragranuloma) Supradiaphragmatic Ann Arbor clinical stage I or II Previously untreated Age 15-70 years WHO performance 0-3 FDG-PET scan prospectively planned after two cycles of ABVD in all patients Informed consent

Period 1 title

Randomization

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Favorable - Standard

Arm description

ABVD x 2 cycles (28 days each cycle)

Arm type

Active comparator

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Favorable - Experimental

Arm description

ABVD x 2 cycles (28 days each cycle)

Arm type

Experimental

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Unfavorable - Standard

Arm description

ABVD x 2 cycles (28 days each cycle)

Arm type

Active comparator

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Unfavorable - Experimental

Arm description

ABVD x 2 cycles (28 days each cycle)

Arm type

Experimental

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Number of subjects in period 1	Favorable - Standard	Favorable - Experimental	Unfavorable - Standard	Unfavorable - Experimental
Started	375	379	597	599
Completed	371	376	583	595
Not completed	4	3	14	4
Adverse event, serious fatal	-	-	1	1
Physician decision	-	-	3	-
Lost to follow-up	-	-	2	1
Adverse event, non-fatal	-	-	1	-
Protocol deviation	4	3	7	2

Period 2 title

PET after 2 cycles ABVD

Is this the baseline period?

Yes ^[1]

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Favorable - Standard - PET negative

Arm description

ABVD x 1 cycle (28 days) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions)

Arm type

Active comparator

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Favorable - Experimental - PET negative

Arm description

ABVD x 2 cycles (28 days each cycle) without further RT

Arm type

Experimental

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Unfavorable - Standard - PET negative

Arm description

ABVDx2 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions).

Arm type

Active comparator

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Unfavorable - Experimental - PET negative

Arm description

ABVDx 4 cycles (28 days each cycle), without RT

Arm type

Experimental

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Standard - PET positive

Arm description

Favorable : ABVDx1 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions) Unfavorable: ABVDx2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

Arm type

Active comparator

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Experimental - PET positive

Arm description

escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions).

Arm type

Experimental

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Cyclophosphamide 1250 mg/m2 i.v. day 1

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 35 mg/m2 i.v. day 1

Investigational medicinal product name

Vincristine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vincristine 1.4 mg/m2 i.v.(max.2mg) day 8

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 8

Investigational medicinal product name

Etoposide

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Etoposide 200 mg/m2 i.v. day 1 to 3

Investigational medicinal product name

Procacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Procarbazine 100 mg/m2 orally day 1 to 7

Investigational medicinal product name

Prednisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Prednisone 40 mg/m2 orally day 1 to 14

Favorable - PET negative (after amendment 2010)

Arm description

ABVD x 1 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions).

Arm type

Not for comparison

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Unfavorable - PET negative (after amendment 2010)

Arm description

ABVD x 2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

Arm type

Not for comparison

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Doxorubicin 25 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

Investigational medicinal product name

Vinblastine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Vinblastine 6 mg/m2 i.v. day 1 and 15

Investigational medicinal product name

Dacarbazine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Dacarbazine 375 mg/m2 i.v. day 1 and 15

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Period 1 is the period starting at randomization and covers the two first cycles of ABVD. The 3 groups of interest (1) Favorable - PET negative 2) Unfavorable - PET negative 3) PET positive) can only be defined after the PET performed after 2 cycles ABVD, that is, at period 2.

Number of subjects in period 2 ^[2]	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)
Started	227	238	292	302	192	169	185	320
Completed	220	228	276	284	164	139	179	309
Not completed	7	10	16	18	28	30	6	11
Patient refusal	1	2	5	5	2	10	-	2
Adverse event, serious fatal	-	-	-	1	-	-	-	-
Physician decision	3	6	5	8	13	18	2	6
Adverse event, non-fatal	-	1	1	4	-	-	2	2
Unknown reason	1	-	1	-	-	-	2	-
Patient move	1	-	-	-	-	-	-	-
Protocol deviation	1	1	3	-	1	2	-	-
Lack of efficacy	-	-	1	-	12	-	-	1

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Of the total 1950 randomized patients, 4 patients did not start ABVD treatment or no information, 7 patients did not complete the 2 first ABVD cycles and 14 patients completed these 2 ABVD cycles but did not do the subsequent PET scan, thus leaving 1925 patients classified in the 3 groups of interest: 1) Favorable - PET negative 2) Unfavorable - PET negative 3) PET positive. 21 of these patients are included in the adverse events section as they received the background therapy (2 cycles ABVD).

Baseline characteristics

Top of page

Reporting group title

Favorable - Standard - PET negative

Reporting group description

ABVD x 1 cycle (28 days) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions)

Reporting group title

Favorable - Experimental - PET negative

Reporting group description

ABVD x 2 cycles (28 days each cycle) without further RT

Reporting group title

Unfavorable - Standard - PET negative

Reporting group description

ABVDx2 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions).

Reporting group title

Unfavorable - Experimental - PET negative

Reporting group description

ABVDx 4 cycles (28 days each cycle), without RT

Reporting group title

Standard - PET positive

Reporting group description

Reporting group title

Experimental - PET positive

Reporting group description

escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions).

Reporting group title

Favorable - PET negative (after amendment 2010)

Reporting group description

ABVD x 1 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions).

Reporting group title

Unfavorable - PET negative (after amendment 2010)

Reporting group description

ABVD x 2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

Reporting group values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)	Total
Number of subjects	227	238	292	302	192	169	185	320	1925
Age categorical
Units: Subjects
In utero									0
Preterm newborn infants (gestational age < 37 wks)									0
Newborns (0-27 days)									0
Infants and toddlers (28 days-23 months)									0
Children (2-11 years)									0
Adolescents (12-17 years)									0
Adults (18-64 years)									0
From 65-84 years									0
85 years and over									0
Age continuous
Units: years
median (full range (min-max))	31 (15 to 49)	30 (15 to 49)	32 (15 to 70)	31 (16 to 70)	30 (15 to 66)	30 (15 to 70)	28 (16 to 49)	30 (16 to 68)	-
Gender categorical
Units: Subjects
Female	96	124	151	165	94	74	101	181	986
Male	131	114	141	137	98	95	84	139	939
Risk group
Favorable/unfavorable, as collected in CRF.
Units: Subjects
Favorable	224	235	12	12	57	47	185	12	784
Unfavorable	3	3	280	290	135	122	0	308	1141
Ann Arbor stage
Units: Subjects
Stage I	65	76	56	59	47	31	50	44	428
Stage II	161	162	232	243	144	136	134	276	1488
Stage III	1	0	2	0	1	2	1	0	7
Stage IV	0	0	2	0	0	0	0	0	2
Baseline PET available (yes/no)
Units: Subjects
No	8	11	14	15	14	9	5	8	84
Yes	219	227	278	287	178	160	180	312	1841
PET after 2 cycles ABVD (local assessment)
Units: Subjects
Negative	221	234	279	293	25	17	178	307	1554
Positive	6	3	13	9	167	152	6	13	369
Missing	0	1	0	0	0	0	1	0	2
PET after 2 cycles ABVD (central review)
Units: Subjects
Negative	164	181	222	227	13	6	122	243	1178
Positive	3	2	7	6	117	127	4	4	270
Unknown/missing	60	55	63	69	62	36	59	73	477
Histology
Units: Subjects
Nodular Lymphocyte Predominant	0	2	0	0	0	0	0	1	3
Nodular Sclerosis	175	175	252	249	148	135	149	285	1568
Mixed Cellularity	36	45	30	29	20	15	23	23	221
Lymphocyte Depletion	2	0	1	3	2	2	2	3	15
Lymphocyte Rich Classical	11	11	4	9	13	7	8	3	66
Other	3	5	5	12	9	10	3	5	52
WHO performance status
Units: Subjects
WHO PS 0	209	230	239	239	147	125	169	253	1611
WHO PS 1	18	7	51	60	44	41	14	63	298
WHO PS 2	0	1	2	3	1	3	2	3	15
WHO PS 3	0	0	0	0	0	0	0	1	1

End points

Top of page

Reporting group title

Favorable - Standard

Reporting group description

ABVD x 2 cycles (28 days each cycle)

Reporting group title

Favorable - Experimental

Reporting group description

ABVD x 2 cycles (28 days each cycle)

Reporting group title

Unfavorable - Standard

Reporting group description

ABVD x 2 cycles (28 days each cycle)

Reporting group title

Unfavorable - Experimental

Reporting group description

ABVD x 2 cycles (28 days each cycle)

Reporting group title

Favorable - Standard - PET negative

Reporting group description

ABVD x 1 cycle (28 days) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions)

Reporting group title

Favorable - Experimental - PET negative

Reporting group description

ABVD x 2 cycles (28 days each cycle) without further RT

Reporting group title

Unfavorable - Standard - PET negative

Reporting group description

ABVDx2 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions).

Reporting group title

Unfavorable - Experimental - PET negative

Reporting group description

ABVDx 4 cycles (28 days each cycle), without RT

Reporting group title

Standard - PET positive

Reporting group description

Reporting group title

Experimental - PET positive

Reporting group description

escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions).

Reporting group title

Favorable - PET negative (after amendment 2010)

Reporting group description

ABVD x 1 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions).

Reporting group title

Unfavorable - PET negative (after amendment 2010)

Reporting group description

ABVD x 2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

Primary: PFS rate at 5 years (%) - Study population

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End point title

PFS rate at 5 years (%) - Study population ^[1]

End point description

Progression free survival (PFS) is counted from the date of randomization to the date of documentation of objective progression or death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.

End point type

Primary

End point timeframe

Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.

End point values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive
Number of subjects analysed	227	238	292	302	192	169
Units: Percentage
number (not applicable)	99	87.1	92.1	89.6	77.4	90.6

Comparison Favorable PET negative: Exp vs. Std

Comparison groups

Favorable - Experimental - PET negative v Favorable - Standard - PET negative

Number of subjects included in analysis

465

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.986 ^[2]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

15.81

Confidence interval

level

95%

sides

2-sided

lower limit

3.79

upper limit

66.07

Notes
[2] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=3.2 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test

Comparison Unfavorable PET negative: Exp vs. Std

Comparison groups

Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.908 ^[3]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.5

Notes
[3] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=2.1 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test

Comparison PET positive: Exp vs. Std

Comparison groups

Standard - PET positive v Experimental - PET positive

Number of subjects included in analysis

361

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

0.74

Secondary: EFS rate at 5 years (%) - Study population

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End point title

EFS rate at 5 years (%) - Study population ^[4]

End point description

Event free survival (EFS) is counted from the date of randomization to the date of occurrence of death, objective progression, premature discontinuation of protocol therapy, or start of off protocol anti-cancer therapy. Patients without documented event at the time of the analysis are censored at the date of last follow-up. It was agreed by the DRC that off protocol anti-cancer therapy was to be restricted to therapy for HL; therapy for second malignancies was not considered as an event for EFS by the DRC. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.

End point type

Secondary

End point timeframe

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.

End point values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive
Number of subjects analysed	227	238	292	302	192	169
Units: Percentage
number (not applicable)	96.3	82.5	87	82.7	71	76.5

Comparison Favorable PET negative: Exp vs. Std

Comparison groups

Favorable - Standard - PET negative v Favorable - Experimental - PET negative

Number of subjects included in analysis

465

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Parameter type

Hazard ratio (HR)

Point estimate

5.33

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

11.36

Notes
[5] - No inferential test as non-inferiority margin for EFS not pre-specified.

Comparison Unfavorable PET negative: Exp vs. Std

Comparison groups

Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

other ^[6]

Method

Parameter type

Hazard ratio (HR)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

2.17

Notes
[6] - No inferential test as non-inferiority margin for EFS not pre-specified.

Comparison PET positive: Exp vs. Std

Comparison groups

Standard - PET positive v Experimental - PET positive

Number of subjects included in analysis

361

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.417

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.27

Secondary: OS rate at 5 years (%) - Study population

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End point title

OS rate at 5 years (%) - Study population ^[7]

End point description

Overall survival (OS) is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.

End point type

Secondary

End point timeframe

Overall survival is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up.

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.

End point values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive
Number of subjects analysed	227	238	292	302	192	169
Units: Percentage
number (not applicable)	100	99.6	96.7	99.3	89.3	96

Comparison PET positive: Exp vs. Std

Comparison groups

Standard - PET positive v Experimental - PET positive

Number of subjects included in analysis

361

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

1.07

Comparison Unfavorable PET negative: Exp vs. Std

Comparison groups

Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

other ^[8]

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

1.58

Notes
[8] - No inferential test as non-inferiority margin for OS not pre-specified.

Secondary: PFS rate at 5 years (%) - Per-protocol population

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End point title

PFS rate at 5 years (%) - Per-protocol population ^[9]

End point description

Progression free survival (PFS) is counted from the date of randomization to the date of documentation of objective progression or death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the per-protocol population: all "study" patients who were eligible for the trial, excluding patients who were later found to be in the wrong risk group (favorable/unfavorable; PET negative/positive).

End point type

Secondary

End point timeframe

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.

End point values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive
Number of subjects analysed	221	232	268	289	172	159
Units: Percentage
number (not applicable)	98.9	88.6	91.7	89.8	75.9	91.9

Comparison Favorable PET negative: Exp vs. Std

Comparison groups

Favorable - Standard - PET negative v Favorable - Experimental - PET negative

Number of subjects included in analysis

453

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.976 ^[10]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

13.68

Confidence interval

level

95%

sides

2-sided

lower limit

3.25

upper limit

57.55

Notes
[10] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=3.2 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test

Comparison Unfavorable PET negative: Exp vs. Std

Comparison groups

Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative

Number of subjects included in analysis

557

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.948 ^[11]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

2.31

Notes
[11] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=2.1 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test

Comparison PET positive: Exp vs. Std

Comparison groups

Standard - PET positive v Experimental - PET positive

Number of subjects included in analysis

331

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

0.62

Secondary: EFS rate at 5 years (%) - Per-protocol population

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End point title

EFS rate at 5 years (%) - Per-protocol population ^[12]

End point description

Event free survival (EFS) is counted from the date of randomization to the date of occurrence of death, objective progression, premature discontinuation of protocol therapy, or start of off protocol anti-cancer therapy. Patients without documented event at the time of the analysis are censored at the date of last follow-up. It was agreed by the DRC that off protocol anti-cancer therapy was to be restricted to therapy for HL; therapy for second malignancies was not considered as an event for EFS by the DRC. Endpoint analyzed in the per-protocol population: all "study" patients who were eligible for the trial, excluding patients who were later found to be in the wrong risk group (favorable/unfavorable; PET negative/positive).

End point type

Secondary

End point timeframe

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.

End point values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive
Number of subjects analysed	221	232	268	289	172	159
Units: Percentage
number (not applicable)	96.7	84.3	87.6	83.6	71.7	78.8

Comparison Favorable PET negative: Exp vs. Std

Comparison groups

Favorable - Standard - PET negative v Favorable - Experimental - PET negative

Number of subjects included in analysis

453

Analysis specification

Pre-specified

Analysis type

other ^[13]

Method

Parameter type

Hazard ratio (HR)

Point estimate

5.34

Confidence interval

level

95%

sides

2-sided

lower limit

2.38

upper limit

11.98

Notes
[13] - No inferential test as non-inferiority margin for EFS not pre-specified.

Comparison Unfavorable PET negative: Exp vs. Std

Comparison groups

Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative

Number of subjects included in analysis

557

Analysis specification

Pre-specified

Analysis type

other ^[14]

Method

Parameter type

Hazard ratio (HR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

2.2

Notes
[14] - No inferential test as non-inferiority margin for EFS not pre-specified.

Comparison PET positive: Exp vs. Std

Comparison groups

Standard - PET positive v Experimental - PET positive

Number of subjects included in analysis

331

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.262

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.21

Secondary: OS rate at 5 years (%) - Per-protocol population

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End point title

OS rate at 5 years (%) - Per-protocol population ^[15]

End point description

Overall survival (OS) is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the per-protocol population: all "study" patients who were eligible for the trial, excluding patients who were later found to be in the wrong risk group (favorable/unfavorable; PET negative/positive).

End point type

Secondary

End point timeframe

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.

End point values	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive
Number of subjects analysed	221	232	268	289	172	159
Units: Percentage
number (not applicable)	100	99.6	96.4	98.2	89.3	95.7

Comparison PET positive: Exp vs. Std

Comparison groups

Standard - PET positive v Experimental - PET positive

Number of subjects included in analysis

331

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.097

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

1.16

Comparison Unfavorable PET negative: Exp vs. Std

Comparison groups

Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative

Number of subjects included in analysis

557

Analysis specification

Pre-specified

Analysis type

other ^[16]

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

1.35

Notes
[16] - No inferential test as non-inferiority margin for OS not pre-specified.

Secondary: PFS rate at 3 years (%) - Study population

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End point title

PFS rate at 3 years (%) - Study population ^[17]

End point description

End point type

Secondary

End point timeframe

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint (at 3 years) is not provided for the arms where the same endpoint at 5 years is provided.

End point values	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)
Number of subjects analysed	185	320
Units: Percentage
number (not applicable)	98.9	95.5

No statistical analyses for this end point

Secondary: EFS rate at 3 years (%) - Study population

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End point title

EFS rate at 3 years (%) - Study population ^[18]

End point description

End point type

Secondary

End point timeframe

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint (at 3 years) is not provided for the arms where the same endpoint at 5 years is provided.

End point values	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)
Number of subjects analysed	185	320
Units: Percentage
number (not applicable)	96.7	93.6

No statistical analyses for this end point

Secondary: OS rate at 3 years (%) - Study population

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End point title

OS rate at 3 years (%) - Study population ^[19]

End point description

End point type

Secondary

End point timeframe

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint (at 3 years) is not provided for the arms where the same endpoint at 5 years is provided.

End point values	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)
Number of subjects analysed	185	320
Units: Percentage
number (not applicable)	100	99.7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events and results of blood tests/ serum chemistry were collected on a CRF to be submitted at pre-specified time-points: before treatment start; after each cycle of CT; at end of CT; at end of RT; during follow-up.

Adverse event reporting additional description

CRF for AEs contains pre-specified items + additional boxes for all "other" AEs. (Few AEs are reported as "other" and are not reported as not available from the list of SOC). AEs are evaluated using CTC grading, SAEs using MedDra. Non-SAEs has not been collected specifically, therefore all AEs (grade 3 or more) will be reported in non-SAE section.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Favorable - Standard - PET negative

Reporting group description

ABVD x 3 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

Reporting group title

Favorable - Experimental - PET negative

Reporting group description

ABVD x 4 cycles (28 days each cycle) without further RT. Safety population: Patients who started the allocated treatment.

Reporting group title

Unfavorable - Standard - PET negative

Reporting group description

ABVD x 4 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

Reporting group title

Unfavorable - Experimental - PET negative

Reporting group description

ABVD x 6 cycles (28 days each cycle), without RT. Safety population: Patients who started the allocated treatment.

Reporting group title

Standard - PET positive

Reporting group description

Favorable : ABVDx3 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions) Unfavorable: ABVDx4 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

Reporting group title

Experimental - PET positive

Reporting group description

ABVD x 2 cycles (28 days each cycle) + escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

Reporting group title

Favorable - PET negative (after amendment 2010)

Reporting group description

ABVD x 3 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions). Safety population: Patients who started the allocated treatment.

Reporting group title

Unfavorable - PET negative (after amendment 2010)

Reporting group description

ABVD x 4 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

Reporting group title

No PET after 2 cycles

Reporting group description

Started ABVD treatment but no PET after 2 cycles.

Serious adverse events	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)	No PET after 2 cycles
Total subjects affected by serious adverse events
subjects affected / exposed	15 / 227 (6.61%)	18 / 238 (7.56%)	38 / 292 (13.01%)	47 / 302 (15.56%)	17 / 192 (8.85%)	42 / 169 (24.85%)	15 / 185 (8.11%)	31 / 320 (9.69%)	3 / 21 (14.29%)
number of deaths (all causes)	0	3	10	6	18	7	0	1	3
number of deaths resulting from adverse events	0	0	0	1	0	1	0	0	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	3 / 292 (1.03%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 1	0 / 0	2 / 3	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Jugular vein thrombosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Phlebitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombophlebitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	2 / 302 (0.66%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 2	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Catheter site inflammation
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chills
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	2 / 320 (0.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related thrombosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inflammation
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza like illness
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion site extravasation
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malaise
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mucosal inflammation
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	2 / 169 (1.18%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
Additional description: From pharmacovigilance database.
subjects affected / exposed	3 / 227 (1.32%)	1 / 238 (0.42%)	2 / 292 (0.68%)	6 / 302 (1.99%)	0 / 192 (0.00%)	9 / 169 (5.33%)	1 / 185 (0.54%)	6 / 320 (1.88%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	2 / 3	1 / 1	1 / 2	5 / 6	0 / 0	8 / 11	0 / 1	4 / 6	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sense of oppression
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Contrast media allergy
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Prostatitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pruritus genital
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory distress syndrome
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung disorder
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	4 / 302 (1.32%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	4 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung infiltration
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oropharyngeal pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Painful respiration
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	4 / 292 (1.37%)	4 / 302 (1.32%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	4 / 4	4 / 4	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	2 / 292 (0.68%)	2 / 302 (0.66%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	5 / 292 (1.71%)	3 / 302 (0.99%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	1 / 320 (0.31%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 6	0 / 3	0 / 0	0 / 0	0 / 1	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Pulmonary toxicity
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	2 / 302 (0.66%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Psychiatric disorders
Anxiety
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	2 / 302 (0.66%)	0 / 192 (0.00%)	2 / 169 (1.18%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 2	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Insomnia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	2 / 302 (0.66%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Maternal exposure before pregnancy
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis chemical
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural complication
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural fistula
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiation dysphagia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiation oesophagitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Coronary artery stenosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intracardiac thrombus
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	2 / 292 (0.68%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Left ventricular dysfunction
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-obstructive cardiomyopathy
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Palpitations
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericarditis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinus tachycardia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral infarction
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral venous thrombosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coma
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lhermitte's sign
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental impairment
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tremor
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	2 / 302 (0.66%)	0 / 192 (0.00%)	2 / 169 (1.18%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone marrow failure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	3 / 169 (1.78%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	3 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile bone marrow aplasia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	4 / 169 (2.37%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	4 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
Additional description: From pharmacovigilance database.
subjects affected / exposed	3 / 227 (1.32%)	3 / 238 (1.26%)	2 / 292 (0.68%)	6 / 302 (1.99%)	0 / 192 (0.00%)	17 / 169 (10.06%)	6 / 185 (3.24%)	5 / 320 (1.56%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	3 / 3	3 / 3	2 / 2	6 / 6	0 / 0	17 / 18	8 / 8	5 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
Additional description: From pharmacovigilance database.
subjects affected / exposed	2 / 227 (0.88%)	0 / 238 (0.00%)	4 / 292 (1.37%)	3 / 302 (0.99%)	1 / 192 (0.52%)	3 / 169 (1.78%)	1 / 185 (0.54%)	3 / 320 (0.94%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	4 / 4	6 / 6	1 / 1	4 / 4	1 / 1	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	4 / 169 (2.37%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	4 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	2 / 169 (1.18%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombotic microangiopathy
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Oculogyric crisis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	1 / 185 (0.54%)	2 / 320 (0.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	2 / 302 (0.66%)	1 / 192 (0.52%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 2	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fissure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fistula
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal inflammation
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colonic pseudo-obstruction
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
Additional description: From pharmacovigilance database.
subjects affected / exposed	2 / 227 (0.88%)	3 / 238 (1.26%)	1 / 292 (0.34%)	0 / 302 (0.00%)	2 / 192 (1.04%)	3 / 169 (1.78%)	1 / 185 (0.54%)	0 / 320 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	2 / 2	3 / 3	2 / 2	0 / 0	2 / 2	2 / 3	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Faecaloma
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematochezia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus paralytic
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
Additional description: From pharmacovigilance database.
subjects affected / exposed	2 / 227 (0.88%)	3 / 238 (1.26%)	1 / 292 (0.34%)	2 / 302 (0.66%)	0 / 192 (0.00%)	3 / 169 (1.78%)	0 / 185 (0.00%)	2 / 320 (0.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	2 / 2	3 / 3	1 / 1	2 / 2	0 / 0	4 / 4	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Proctalgia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	3 / 238 (1.26%)	2 / 292 (0.68%)	1 / 302 (0.33%)	1 / 192 (0.52%)	1 / 169 (0.59%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 1	3 / 3	2 / 2	1 / 1	1 / 1	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Drug-induced liver injury
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic steatosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Hyperhidrosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxic skin eruption
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis haemorrhagic
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hyperaldosteronism
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	3 / 169 (1.78%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle contracture
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal pain
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Anal abscess
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	2 / 292 (0.68%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial sepsis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Bronchitis viral
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopulmonary aspergillosis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter gastroenteritis
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	2 / 292 (0.68%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 2	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related sepsis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	1 / 292 (0.34%)	1 / 302 (0.33%)	1 / 192 (0.52%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterobacter sepsis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
Additional description: From pharmacovigilance database.
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Implant site infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Klebsiella infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Measles
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle abscess
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis streptococcal
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	2 / 292 (0.68%)	4 / 302 (1.32%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	3 / 320 (0.94%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 2	2 / 4	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis Escherichia coli
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhinitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	2 / 169 (1.18%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	2 / 292 (0.68%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vestibular neuronitis
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	2 / 302 (0.66%)	1 / 192 (0.52%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertriglyceridaemia
Additional description: From pharmacovigilance database.
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Favorable - Standard - PET negative	Favorable - Experimental - PET negative	Unfavorable - Standard - PET negative	Unfavorable - Experimental - PET negative	Standard - PET positive	Experimental - PET positive	Favorable - PET negative (after amendment 2010)	Unfavorable - PET negative (after amendment 2010)	No PET after 2 cycles
Total subjects affected by non serious adverse events
subjects affected / exposed	148 / 227 (65.20%)	178 / 238 (74.79%)	222 / 292 (76.03%)	216 / 302 (71.52%)	138 / 192 (71.88%)	142 / 169 (84.02%)	124 / 185 (67.03%)	232 / 320 (72.50%)	12 / 21 (57.14%)
Vascular disorders
Vascular
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	1 / 227 (0.44%)	4 / 238 (1.68%)	11 / 292 (3.77%)	12 / 302 (3.97%)	1 / 192 (0.52%)	1 / 169 (0.59%)	5 / 185 (2.70%)	5 / 320 (1.56%)	2 / 21 (9.52%)
occurrences all number	3	4	19	17	1	1	8	5	2
Surgical and medical procedures
Surgery/Intra-operative injury
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
General disorders and administration site conditions
Constitutional Symptoms
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	7 / 227 (3.08%)	4 / 238 (1.68%)	10 / 292 (3.42%)	16 / 302 (5.30%)	1 / 192 (0.52%)	4 / 169 (2.37%)	1 / 185 (0.54%)	6 / 320 (1.88%)	2 / 21 (9.52%)
occurrences all number	9	4	11	23	1	6	1	6	2
Immune system disorders
Allergy/Immunology
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	0	1	1	0	1	0	0	1
Reproductive system and breast disorders
Sexual/Reproductive function
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	1 / 292 (0.34%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences all number	0	1	1	0	0	1	0	1	0
Respiratory, thoracic and mediastinal disorders
Pulmonary
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	6 / 227 (2.64%)	4 / 238 (1.68%)	24 / 292 (8.22%)	27 / 302 (8.94%)	9 / 192 (4.69%)	9 / 169 (5.33%)	0 / 185 (0.00%)	19 / 320 (5.94%)	1 / 21 (4.76%)
occurrences all number	6	5	27	34	9	9	0	24	1
Investigations
Alkaline phosphatase
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
ANC
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	127 / 227 (55.95%)	159 / 238 (66.81%)	195 / 292 (66.78%)	184 / 302 (60.93%)	122 / 192 (63.54%)	124 / 169 (73.37%)	107 / 185 (57.84%)	200 / 320 (62.50%)	9 / 21 (42.86%)
occurrences all number	307	402	522	583	280	315	226	457	23
Bilirubin
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	5 / 227 (2.20%)	5 / 238 (2.10%)	6 / 292 (2.05%)	5 / 302 (1.66%)	2 / 192 (1.04%)	4 / 169 (2.37%)	8 / 185 (4.32%)	8 / 320 (2.50%)	0 / 21 (0.00%)
occurrences all number	54	23	28	29	44	18	76	119	0
GGT
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	6 / 227 (2.64%)	3 / 238 (1.26%)	9 / 292 (3.08%)	14 / 302 (4.64%)	4 / 192 (2.08%)	4 / 169 (2.37%)	0 / 185 (0.00%)	6 / 320 (1.88%)	0 / 21 (0.00%)
occurrences all number	8	3	17	34	6	4	0	8	0
Platelets
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	1 / 227 (0.44%)	2 / 238 (0.84%)	1 / 292 (0.34%)	5 / 302 (1.66%)	3 / 192 (1.56%)	29 / 169 (17.16%)	1 / 185 (0.54%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	3	1	6	3	43	1	0	0
Serum creatinine
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	3 / 227 (1.32%)	4 / 238 (1.68%)	2 / 292 (0.68%)	3 / 302 (0.99%)	2 / 192 (1.04%)	2 / 169 (1.18%)	9 / 185 (4.86%)	8 / 320 (2.50%)	0 / 21 (0.00%)
occurrences all number	52	21	24	27	44	16	78	119	0
SGOT(ASAT)
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	1 / 302 (0.33%)	3 / 192 (1.56%)	1 / 169 (0.59%)	1 / 185 (0.54%)	2 / 320 (0.63%)	0 / 21 (0.00%)
occurrences all number	0	0	1	1	3	1	1	2	0
SGPT(ALAT)
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	2 / 227 (0.88%)	6 / 238 (2.52%)	5 / 292 (1.71%)	6 / 302 (1.99%)	3 / 192 (1.56%)	1 / 169 (0.59%)	2 / 185 (1.08%)	5 / 320 (1.56%)	0 / 21 (0.00%)
occurrences all number	3	13	6	7	3	2	3	6	0
White Blood Cells
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	30 / 227 (13.22%)	42 / 238 (17.65%)	64 / 292 (21.92%)	63 / 302 (20.86%)	36 / 192 (18.75%)	107 / 169 (63.31%)	22 / 185 (11.89%)	55 / 320 (17.19%)	2 / 21 (9.52%)
occurrences all number	47	67	112	126	56	221	30	95	2
Cardiac disorders
Cardiac Arrhythmia
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	1 / 320 (0.31%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Cardiac General
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	2 / 292 (0.68%)	4 / 302 (1.32%)	0 / 192 (0.00%)	2 / 169 (1.18%)	2 / 185 (1.08%)	3 / 320 (0.94%)	2 / 21 (9.52%)
occurrences all number	0	0	2	7	0	6	2	3	3
Cardiovascular
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	2 / 227 (0.88%)	0 / 238 (0.00%)	3 / 292 (1.03%)	2 / 302 (0.66%)	2 / 192 (1.04%)	1 / 169 (0.59%)	2 / 185 (1.08%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	0	3	2	2	1	2	0	0
Nervous system disorders
Neurology
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	2 / 227 (0.88%)	3 / 238 (1.26%)	5 / 292 (1.71%)	15 / 302 (4.97%)	4 / 192 (2.08%)	0 / 169 (0.00%)	5 / 185 (2.70%)	3 / 320 (0.94%)	0 / 21 (0.00%)
occurrences all number	3	6	7	24	5	0	5	3	0
Blood and lymphatic system disorders
Blood/Bone Marrow
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	2 / 227 (0.88%)	0 / 238 (0.00%)	6 / 292 (2.05%)	4 / 302 (1.32%)	1 / 192 (0.52%)	14 / 169 (8.28%)	2 / 185 (1.08%)	4 / 320 (1.25%)	0 / 21 (0.00%)
occurrences all number	2	0	6	7	1	17	2	4	0
Febrile neutropenia
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	9 / 227 (3.96%)	11 / 238 (4.62%)	7 / 292 (2.40%)	15 / 302 (4.97%)	6 / 192 (3.13%)	36 / 169 (21.30%)	11 / 185 (5.95%)	17 / 320 (5.31%)	1 / 21 (4.76%)
occurrences all number	11	13	7	16	7	41	12	19	1
Hemoglobin
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	1 / 227 (0.44%)	0 / 238 (0.00%)	0 / 292 (0.00%)	2 / 302 (0.66%)	4 / 192 (2.08%)	9 / 169 (5.33%)	1 / 185 (0.54%)	3 / 320 (0.94%)	0 / 21 (0.00%)
occurrences all number	1	0	0	4	4	12	1	3	0
Lymphatics
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	3 / 302 (0.99%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0
Ear and labyrinth disorders
Auditory/Hearing
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Eye disorders
Ocular/Visual
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	1 / 302 (0.33%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Gastrointestinal disorders
Gastrointestinal
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	10 / 227 (4.41%)	13 / 238 (5.46%)	16 / 292 (5.48%)	11 / 302 (3.64%)	8 / 192 (4.17%)	13 / 169 (7.69%)	9 / 185 (4.86%)	15 / 320 (4.69%)	1 / 21 (4.76%)
occurrences all number	10	15	17	20	10	15	11	16	2
Hepatobiliary disorders
Hepatobiliary/Pancreas
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	1 / 238 (0.42%)	0 / 292 (0.00%)	0 / 302 (0.00%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatology/Skin
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	11 / 227 (4.85%)	10 / 238 (4.20%)	14 / 292 (4.79%)	15 / 302 (4.97%)	9 / 192 (4.69%)	8 / 169 (4.73%)	3 / 185 (1.62%)	1 / 320 (0.31%)	1 / 21 (4.76%)
occurrences all number	31	25	26	36	15	18	4	1	2
Endocrine disorders
Endocrine
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	1 / 292 (0.34%)	0 / 302 (0.00%)	1 / 192 (0.52%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	5	0	2	1	0	0	0
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft tissue
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	0 / 227 (0.00%)	0 / 238 (0.00%)	0 / 292 (0.00%)	3 / 302 (0.99%)	0 / 192 (0.00%)	0 / 169 (0.00%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	10	0	0	0	0	0
Infections and infestations
Infection
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	5 / 227 (2.20%)	4 / 238 (1.68%)	13 / 292 (4.45%)	14 / 302 (4.64%)	3 / 192 (1.56%)	15 / 169 (8.88%)	1 / 185 (0.54%)	9 / 320 (2.81%)	1 / 21 (4.76%)
occurrences all number	6	4	14	17	3	19	1	10	1
Metabolism and nutrition disorders
Albumin
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	2 / 227 (0.88%)	2 / 238 (0.84%)	2 / 292 (0.68%)	4 / 302 (1.32%)	2 / 192 (1.04%)	1 / 169 (0.59%)	1 / 185 (0.54%)	5 / 320 (1.56%)	0 / 21 (0.00%)
occurrences all number	2	2	2	5	2	1	1	7	0
Metabolic/Laboratory
Additional description: From clinical database. All AEs (grade 3 or more).
alternative dictionary used: CTC AE 3.0
subjects affected / exposed	1 / 227 (0.44%)	1 / 238 (0.42%)	2 / 292 (0.68%)	3 / 302 (0.99%)	1 / 192 (0.52%)	1 / 169 (0.59%)	0 / 185 (0.00%)	0 / 320 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	1	2	4	2	2	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 Dec 2011

Purpose: to formalize the agreements with the EORTC IDMC following the pre-planned interim analysis. 1) Recruitment in the trial was to continue until 355 patients with FDG-PET positive after two cycles of ABVD were enrolled, in order to be able to answer the second objective of the study. 2) All patients (including those randomized in the EXP arm) who were FDG-PET negative after two cycles of ABVD were to receive the standard combined modality treatment arm.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/24637998

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Clinical trials

Clinical Trial Results:
The H10 EORTC/GELA/IIL randomized Intergroup trial on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in patients with supradiaphragmatic stage I/II Hodgkin's lymphoma.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS rate at 5 years (%) - Study population

Primary: PFS rate at 5 years (%) - Study population

Secondary: EFS rate at 5 years (%) - Study population

Secondary: EFS rate at 5 years (%) - Study population

Secondary: OS rate at 5 years (%) - Study population

Secondary: OS rate at 5 years (%) - Study population

Secondary: PFS rate at 5 years (%) - Per-protocol population

Secondary: PFS rate at 5 years (%) - Per-protocol population

Secondary: EFS rate at 5 years (%) - Per-protocol population

Secondary: EFS rate at 5 years (%) - Per-protocol population

Secondary: OS rate at 5 years (%) - Per-protocol population

Secondary: OS rate at 5 years (%) - Per-protocol population

Secondary: PFS rate at 3 years (%) - Study population

Secondary: PFS rate at 3 years (%) - Study population

Secondary: EFS rate at 3 years (%) - Study population

Secondary: EFS rate at 3 years (%) - Study population

Secondary: OS rate at 3 years (%) - Study population

Secondary: OS rate at 3 years (%) - Study population

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

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Clinical trials

Clinical Trial Results: The H10 EORTC/GELA/IIL randomized Intergroup trial on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in patients with supradiaphragmatic stage I/II Hodgkin's lymphoma.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS rate at 5 years (%) - Study population

Primary: PFS rate at 5 years (%) - Study population

Secondary: EFS rate at 5 years (%) - Study population

Secondary: EFS rate at 5 years (%) - Study population

Secondary: OS rate at 5 years (%) - Study population

Secondary: OS rate at 5 years (%) - Study population

Secondary: PFS rate at 5 years (%) - Per-protocol population

Secondary: PFS rate at 5 years (%) - Per-protocol population

Secondary: EFS rate at 5 years (%) - Per-protocol population

Secondary: EFS rate at 5 years (%) - Per-protocol population

Secondary: OS rate at 5 years (%) - Per-protocol population

Secondary: OS rate at 5 years (%) - Per-protocol population

Secondary: PFS rate at 3 years (%) - Study population

Secondary: PFS rate at 3 years (%) - Study population

Secondary: EFS rate at 3 years (%) - Study population

Secondary: EFS rate at 3 years (%) - Study population

Secondary: OS rate at 3 years (%) - Study population

Secondary: OS rate at 3 years (%) - Study population

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
The H10 EORTC/GELA/IIL randomized Intergroup trial on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in patients with supradiaphragmatic stage I/II Hodgkin's lymphoma.