Clinical Trial Results:
Evaluation of predictive Factors for the Effectivity of Aromatase Inhibitor Therapy - Offene, prospektive, multizentrische Phase IV-Studie zur Untersuchung des Einflusses von pharmakogenetischen Markern auf die Wirksamkeit und Nebenwirkungsrate bei postmenopausalen, steroidhormonrezeptorpositiven Mammakarzinomspatientinnen, die mit Letrozol behandelt werden.

Trial information Top of page
Trial identification
Sponsor protocol code	TRAFO001
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01908556
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Institut für Frauengesundheit GmbH
Sponsor organisation address	Universitätsstraße 21-23, Erlangen, Germany, 91054
Public contact	Clinical Trials Information, Institut für Frauengesundheit GmbH, +49 091318536167, preface@ifg-erlangen.de
Scientific contact	Clinical Trials Information, Institut für Frauengesundheit GmbH, +49 091318536167, preface@ifg-erlangen.de
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	02 Dec 2024
Is this the analysis of the primary completion data?	Yes
Primary completion date	04 Jan 2016
Global end of trial reached?	Yes
Global end of trial date	04 Jan 2016
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	•Disease free survival in association with tested genotypes (whole genome scan)
Protection of trial subjects	The clinical trial was conducted in accordance with current ethical standards, the Declaration of Helsinki from 1996 and the Guidelines of the International Conference on Harmonization Good Clinical Practice (GCP).
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	26 Feb 2009
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Germany: 3297
Worldwide total number of subjects	3297
EEA total number of subjects	3297
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	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)	1812
From 65 to 84 years	1472
85 years and over	13

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Start of recruitment was on 06-Feb-2009. The clinical trial was conducted in 220 trial sites in Germany. The first patient was enrolled, the last patient was enrolled on 04-Jan-2011. The end of trial was reached 60 months after enrollment of the last patient on 04-Jan-2016. Date of database lock was 08-Feb-2022.
Pre-assignment
Screening details	A total of 3529 patients were registered in the trial and were evaluated for eligibility. 46 patients were identified as screening failures. 102 patients were excluded as they had not started study intervention and 84 patients were excluded as lost to follow-up after screening. Therefore, 3297 patients were assessed.
Period 1
Period 1 title	Overall period
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Blinding implementation details	The trial was open-label
Arms
Arm title	Letrozole
Arm description	Patients received regular letrozole 2.5 mg per day, p.o. for a maximum observation period of five years according to SmPC of letrozole.
Arm type	Experimental
Investigational medicinal product name	Letrozole
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Patients received a daily dose of 2.5mg letrozol film-coated tablets, oral use.
Number of subjects in period 1 Letrozole Started 3297 Completed 1318 Not completed 1979      unknown 605      Irregular end of treatment 1374

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall period
Reporting group description	-
Reporting group values Overall period Total Number of subjects 3297 3297 Age categorical Units: Subjects     < 65 1812 1812     ≥ 65 1472 1472     missing 13 13 Age continuous Units: years     arithmetic mean (standard deviation) 63.9 ( 7.6 ) - Gender categorical All patients enrolled were female Units: Subjects     Female 3297 3297     Male 0 0 BMI Units: Subjects     < 20 124 124     20-25 1097 1097     25-30 1246 1246     ≥ 30 790 790     missing 40 40 pN Pathological lymph node status Units: Subjects     pN0 2312 2312     pN+ 949 949     missing 36 36 pT pathological tumor stage Units: Subjects     pT0 45 45     pT1 2081 2081     pT2 991 991     pT3 120 120     pT4 42 42     missing 18 18 Grading Tumor grading Units: Subjects     G1 603 603     G2 2123 2123     G3 556 556     missing 15 15 ER status estrogen receptor status Units: Subjects     ER- 41 41     ER+ 3241 3241     missing 15 15 PgR progesterone receptor status Units: Subjects     PgR- 456 456     PgR+ 2828 2828     missing 13 13 HR Combined hormone receptor status Units: Subjects     ER-/PgR- 7 7     ER-/PgR+ 34 34     ER+/PgR- 448 448     ER+/PgR+ 2792 2792     missing 16 16 HER2 HER2 status Units: Subjects     HER2- 2897 2897     HER2+ 353 353     missing 47 47 Histological Subtype Units: Subjects     ductal invasive 2422 2422     ductal lobular 564 564     missing 311 311 Previous chemotherapy Units: Subjects     neoadjuvant 241 241     adjuvant 1086 1086     neoadjuvant and adjuvant 9 9     naive 1917 1917     missing 44 44 BMI Units: kg/m²     arithmetic mean (standard deviation) 27.2 ( 5.1 ) -
Subject analysis sets
Subject analysis set title	Full Analysis Set
Subject analysis set type	Full analysis
Subject analysis set description	The full analysis set comprises of patients included in the clinical trial who have started trial treatment and for whom at least one follow-up visit is available after therapy start.
Subject analysis sets values Full Analysis Set Number of subjects 3297 Age categorical Units: Subjects     < 65 1812     ≥ 65 1472     missing 13 Age continuous Units: years     arithmetic mean (standard deviation) 63.9 ( 7.6 ) Gender categorical All patients enrolled were female Units: Subjects     Female 3297     Male 0 BMI Units: Subjects     < 20 124     20-25 1097     25-30 1246     ≥ 30 790     missing 40 pN Pathological lymph node status Units: Subjects     pN0 2312     pN+ 949     missing 36 pT pathological tumor stage Units: Subjects     pT0 45     pT1 2081     pT2 991     pT3 120     pT4 42     missing 18 Grading Tumor grading Units: Subjects     G1 603     G2 2123     G3 556     missing 15 ER status estrogen receptor status Units: Subjects     ER- 41     ER+ 3241     missing 15 PgR progesterone receptor status Units: Subjects     PgR- 456     PgR+ 2828     missing 13 HR Combined hormone receptor status Units: Subjects     ER-/PgR- 7     ER-/PgR+ 34     ER+/PgR- 448     ER+/PgR+ 2792     missing 16 HER2 HER2 status Units: Subjects     HER2- 2897     HER2+ 353     missing 47 Histological Subtype Units: Subjects     ductal invasive 2422     ductal lobular 564     missing 311 Previous chemotherapy Units: Subjects     neoadjuvant 241     adjuvant 1086     neoadjuvant and adjuvant 9     naive 1917     missing 44 BMI Units: kg/m²     arithmetic mean (standard deviation) 27.2 ( 5.1 )

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Letrozole
Reporting group description	Patients received regular letrozole 2.5 mg per day, p.o. for a maximum observation period of five years according to SmPC of letrozole.
Subject analysis set title	Full Analysis Set
Subject analysis set type	Full analysis
Subject analysis set description	The full analysis set comprises of patients included in the clinical trial who have started trial treatment and for whom at least one follow-up visit is available after therapy start.

End points Top of page

Primary: 2-year DFS rate Top of page
End point title	2-year DFS rate [1]
End point description	Disease-free survival is defined as time between first dose of trial treatment and one of the following end-points, whichever occurred first: death, occurrence of distant metastases, secondary carcinoma, breast cancer recurrence (locally or axillary).
End point type	Primary
End point timeframe	Disease-free survival after 2 years
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical tests were peformed for non-genetic analyses.
End point values Letrozole Full Analysis Set Number of subjects analysed 3297 3297 Units: percent     number (confidence interval 95%) 96 (95 to 97) 96 (95 to 97)
No statistical analyses for this end point

Primary: 2-year DFS rate Top of page

Primary: 3-year DFS rate Top of page
End point title	3-year DFS rate [2]
End point description	Disease-free survival is defined as time between first dose of trial treatment and one of the following end-points, whichever occurred first: death, occurrence of distant metastases, secondary carcinoma, breast cancer recurrence (locally or axillary).
End point type	Primary
End point timeframe	Disease-free survival after 3 years
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical tests were peformed for non-genetic analyses.
End point values Letrozole Full Analysis Set Number of subjects analysed 3297 3297 Units: percent     number (confidence interval 95%) 94 (93 to 95) 94 (93 to 95)
No statistical analyses for this end point

Primary: 3-year DFS rate Top of page

Primary: 5-year DFS rate Top of page
End point title	5-year DFS rate [3]
End point description	Disease-free survival is defined as time between first dose of trial treatment and one of the following end-points, whichever occurred first: death, occurrence of distant metastases, secondary carcinoma, breast cancer recurrence (locally or axillary).
End point type	Primary
End point timeframe	Disease-free survival after 5 years
Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical tests were peformed for non-genetic analyses.
End point values Letrozole Full Analysis Set Number of subjects analysed 3297 3297 Units: percent     number (confidence interval 95%) 89 (88 to 90) 89 (88 to 90)
No statistical analyses for this end point

Primary: 5-year DFS rate Top of page

Secondary: 2-year OS rate Top of page
End point title	2-year OS rate
End point description	Overall survival is defined as time between first dose of trial treatment and patient's death regardless of reason.
End point type	Secondary
End point timeframe	Overall survival after 2 years
End point values Letrozole Full Analysis Set Number of subjects analysed 3297 3297 Units: percent     number (confidence interval 95%) 99 (98 to 99) 99 (98 to 99)
No statistical analyses for this end point

Secondary: 2-year OS rate Top of page

Secondary: 3-year OS rate Top of page
End point title	3-year OS rate
End point description	Overall survival is defined as time between first dose of trial treatment and patient's death regardless of reason.
End point type	Secondary
End point timeframe	Overall survival after 3 years
End point values Letrozole Full Analysis Set Number of subjects analysed 3297 3297 Units: percent     number (confidence interval 95%) 98 (97 to 98) 98 (97 to 98)
No statistical analyses for this end point

Secondary: 3-year OS rate Top of page

Secondary: 5-year OS rate Top of page
End point title	5-year OS rate
End point description	Overall survival is defined as time between first dose of trial treatment and patient's death regardless of reason.
End point type	Secondary
End point timeframe	Overall survival after 5 years
End point values Letrozole Full Analysis Set Number of subjects analysed 3297 3297 Units: percent     number (confidence interval 95%) 95 (94 to 96) 95 (94 to 96)
No statistical analyses for this end point

Secondary: 5-year OS rate Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Time of treatment start until 14 days after last dose of trial treatment
Adverse event reporting additional description	Adverse events are reported for letrozole
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	CTCAE
Dictionary version	3.0
Reporting groups
Reporting group title	Full Analysis Set
Reporting group description	Safety analysis was performed in the full analysis set, including all patients exposed to ribociclib for whom at least one follow-up visit was available. This is justified as no safety data is available for patient for whom only baseline data is avaliable.
Serious adverse events Full Analysis Set Total subjects affected by serious adverse events      subjects affected / exposed 398 / 3297 (12.07%)      number of deaths (all causes) 141      number of deaths resulting from adverse events 28 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy Additional description: Development of a new cancer resulting from treatment from an earlier cancer diagnosis alternative assessment type: Non-systematic      subjects affected / exposed 95 / 3297 (2.88%)      occurrences causally related to treatment / all 1 / 101      deaths causally related to treatment / all 0 / 5 Vascular disorders Peripheral arterial ischemia Additional description: Disorder of arteries causing inadequate blood supply to extremities. alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 1 Thrombosis/thrombus/embolism Additional description: Formation or presence of a blood clot inside a blood vessel. alternative assessment type: Non-systematic      subjects affected / exposed 14 / 3297 (0.42%)      occurrences causally related to treatment / all 4 / 14      deaths causally related to treatment / all 1 / 1 Vascular - Other alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 General disorders and administration site conditions Fatigue Additional description: Fatigue, tiredness, asthenia alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 2 Death Additional description: Death not associated with CTCAE term alternative assessment type: Non-systematic      subjects affected / exposed 14 / 3297 (0.42%)      occurrences causally related to treatment / all 0 / 14      deaths causally related to treatment / all 0 / 14 Chest pain alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Head pain alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 1 / 3      deaths causally related to treatment / all 0 / 0 Pain - Other alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Immune system disorders Allergic reaction/hypersensitivity Additional description: Allergic reaction/hypersensitivity (including drug fever) alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Reproductive system and breast disorders Hemorrhage, GU Additional description: Bleeding of the vagina alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Breast pain alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 1 / 4      deaths causally related to treatment / all 0 / 0 Breast function/lactation Additional description: Change in ability to produce milk from breasts alternative assessment type: Non-systematic      subjects affected / exposed 11 / 3297 (0.33%)      occurrences causally related to treatment / all 0 / 11      deaths causally related to treatment / all 0 / 0 Breast volume/hypoplasia Additional description: Decreased size of breast tissue alternative assessment type: Non-systematic      subjects affected / exposed 9 / 3297 (0.27%)      occurrences causally related to treatment / all 0 / 10      deaths causally related to treatment / all 0 / 0 Sexual/Reproductive Function - Other alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing Additional description: Irritation of the small airways or wheezing alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Cough alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Dyspnea Additional description: Shortness of breath alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences causally related to treatment / all 0 / 6      deaths causally related to treatment / all 0 / 0 Obstruction/stenosis of airway Additional description: Blockage of an air tube from the windpipe to the lungs alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Pleural effusion (non-malignant) Additional description: Collection of fluid between the thin layers of tissue (pleura) lining the lung and the wall of the chest cavity alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 1 / 3      deaths causally related to treatment / all 0 / 0 Pneumonitis/pulmonary infiltrates Additional description: Inflammation of the lungs alternative assessment type: Non-systematic      subjects affected / exposed 11 / 3297 (0.33%)      occurrences causally related to treatment / all 0 / 13      deaths causally related to treatment / all 0 / 0 Pulmonary/Upper Respiratory - Other alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Voice changes/dysarthria Additional description: Voice changes, laryngitis, hoarseness (e.g., hoarseness, loss or alteration in voice, laryngitis) alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Psychiatric disorders Cognitive disturbance Additional description: Disturbances in thinking patterns alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Memory impairment Additional description: Memory impairment alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Mental status Additional description: Changes in mental status alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Mood alteration Additional description: Depression alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Personality/behavioral Additional description: Personality changes alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Investigations Weight gain alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Weight loss alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 ALT, SGPT (serum glutamic pyruvic transaminase) Additional description: Abnormal liver enzyme level alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Bilirubin (hyperbilirubinemia) Additional description: Abnormal level of bilirubin in the blood. Bilirubin is a bile pigment found in the liver. alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Injury, poisoning and procedural complications Intra-operative injury; Arm Additional description: Damage to a part of the body during an operation: Arm alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Intra-operative injury; nose Additional description: Damage to a part of the body during an operation: Nose alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Intra-operative injury; pelvis Additional description: Damage to a part of the body during an operation: Pelvis alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Intra-operative injury; uterus Additional description: Damage to a part of the body during an operation: Uterus alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Intra-operative injury; vagina Additional description: Damage to a part of the body during an operation: Vagina alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Cardiac disorders Cardiac Arrhythmia - Other alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Conduction abnormality/atrioventricular heart block Additional description: Irregular heart beat alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Palpitations Additional description: Feeling the heart racing 'skipping a beat' pounding alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Supraventricular and nodal arrhythmia Additional description: Irregular heart beat alternative assessment type: Non-systematic      subjects affected / exposed 11 / 3297 (0.33%)      occurrences causally related to treatment / all 1 / 12      deaths causally related to treatment / all 0 / 0 Cardiac ischemia/infarction Additional description: Decreased blood supply to the heart/ heart attack alternative assessment type: Non-systematic      subjects affected / exposed 15 / 3297 (0.45%)      occurrences causally related to treatment / all 4 / 17      deaths causally related to treatment / all 0 / 0 Cardiac General - Other alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Cardiopulmonary arrest, cause unknown (non-fatal) Additional description: Heart and lungs stop working alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 1 / 2      deaths causally related to treatment / all 1 / 2 Hypertension Additional description: High blood pressure alternative assessment type: Non-systematic      subjects affected / exposed 9 / 3297 (0.27%)      occurrences causally related to treatment / all 0 / 10      deaths causally related to treatment / all 0 / 0 Left ventricular systolic dysfunction Additional description: Decrease in heart's ability to pump blood alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Restrictive cardiomyopathy Additional description: Decrease in heart's ability to pump blood alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Right ventricular dysfunction (cor pulmonale) Additional description: Decrease in heart's ability to pump blood alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Valvular heart disease Additional description: Abnormal heart valves alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Nervous system disorders Hemorrhage, CNS Additional description: Bleeding into the brain or spinal cord alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Ataxia (incoordination) Additional description: Loss of muscle coordination awkward, uncoordinated walking unsteadiness when walking alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 CNS cerebrovascular ischemia Additional description: Decrease in blood flow to the brain alternative assessment type: Non-systematic      subjects affected / exposed 10 / 3297 (0.30%)      occurrences causally related to treatment / all 0 / 10      deaths causally related to treatment / all 0 / 0 Dizziness Additional description: Dizziness alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Neurology - Other alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences causally related to treatment / all 0 / 6      deaths causally related to treatment / all 0 / 1 Neuropathy: cranial Additional description: Abnormal function of the nerve responsible for feeling in the face and control of the muscles for chewing alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Neuropathy: sensory Additional description: Condition of the nervous system that causes numbness, tingling, burning. alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Syncope (fainting) Additional description: Fainting alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Nerve pain alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Blood and lymphatic system disorders Blood/Bone Marrow - Other alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Hemoglobin Additional description: Decrease in a part of red blood cells that carries oxygen in the body alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Coagulation - Other alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Thrombotic microangiopathy Additional description: Thrombotic microangiopathy (e.g., thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS]). Abnormal clotting of blood in small blood vessels alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Edema: limb Additional description: Swelling of the arms and legs alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Ear and labyrinth disorders Auditory/Ear - Other alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Tinnitus Additional description: Ringing in the ears alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Eye disorders Ocular/Visual - Other alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Retinal detachment Additional description: Separation of the retina from its connection at the back of the eye alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Gastrointestinal disorders Ascites (non-malignant) Fluid collection Additional description: Fluid collection in the abdomen alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Colitis Additional description: Inflammation of the colon alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Gastritis (including bile reflux gastritis) Additional description: Inflammation of the lining of the stomach alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Gastrointestinal - Other alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences causally related to treatment / all 0 / 7      deaths causally related to treatment / all 0 / 0 Heartburn/dyspepsia alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) Additional description: Abnormally slow bowel contraction alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 1 Mucositis/stomatitis (functional/symptomatic) Additional description: Irritation or sores in the lining of the small intestine alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Nausea alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Ulcer, GI Additional description: Ulcer of small intestine alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Vomiting alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Hemorrhage, GI Additional description: Bleeding of the lower digestive tract alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Belly pain alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Stomach pain alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Hepatobiliary disorders Cholecystitis Additional description: Inflammation of the gallbladder alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 1 / 3      deaths causally related to treatment / all 0 / 1 Hepatobiliary/Pancreas - Other alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 5      deaths causally related to treatment / all 0 / 0 Liver dysfunction/failure (clinical) Additional description: Liver problems/liver failure alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Pancreatitis Additional description: Inflammation of the pancreas alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Skin and subcutaneous tissue disorders Atrophy, subcutaneous fat Additional description: Loss of fat under the skin alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Dermatology/Skin - Other alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Flushing Additional description: Sudden reddening of the face and/or neck alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Induration/fibrosis (skin and subcutaneous tissue) Additional description: Hardening of the skin and connective tissues alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Rash/desquamation Additional description: Rash flaking or sloughing of skin alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Rash: dermatitis associated with radiation Additional description: Redness, flaking or sloughing of skin in the radiation treatment area alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Skin breakdown/decubitus ulcer Additional description: Skin sores alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Wound complication, non-infectious Additional description: Wound complication alternative assessment type: Non-systematic      subjects affected / exposed 22 / 3297 (0.67%)      occurrences causally related to treatment / all 0 / 23      deaths causally related to treatment / all 0 / 0 Scalp pain alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Renal and urinary disorders Cystitis Additional description: Inflammation or infection of the bladder alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Incontinence, urinary Additional description: Inability to hold urine in the bladder alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Obstruction, GU Additional description: Blockage of tube between kidney and bladder alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Renal failure Additional description: Kidney failure alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Renal/Genitourinary - Other alternative assessment type: Non-systematic      subjects affected / exposed 9 / 3297 (0.27%)      occurrences causally related to treatment / all 0 / 11      deaths causally related to treatment / all 0 / 0 Urinary retention (including neurogenic bladder) Additional description: Difficulty emptying the bladder alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Endocrine disorders Endocrine - Other alternative assessment type: Non-systematic      subjects affected / exposed 5 / 3297 (0.15%)      occurrences causally related to treatment / all 0 / 5      deaths causally related to treatment / all 0 / 0 Thyroid function, high Additional description: Abnormally high thyroid function (hyperthyroidism, thyrotoxicosis) alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Musculoskeletal and connective tissue disorders Cervical spine-range of motion Additional description: Stiff neck alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Extremity-lower (gait/walking) Additional description: Limp alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Fibrosis-cosmesis Additional description: Scar or thickening alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Fibrosis-deep connective tissue Additional description: Scar or thickening alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Fracture Additional description: A broken bone alternative assessment type: Non-systematic      subjects affected / exposed 37 / 3297 (1.12%)      occurrences causally related to treatment / all 1 / 40      deaths causally related to treatment / all 0 / 0 Joint-function Additional description: Joint stiffness alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Local complication -device/prosthesis-related Additional description: Local complication of an artificial body part or device alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Musculoskeletal/Soft Tissue - Other alternative assessment type: Non-systematic      subjects affected / exposed 12 / 3297 (0.36%)      occurrences causally related to treatment / all 2 / 12      deaths causally related to treatment / all 0 / 0 Osteoporosis Additional description: Bone thinning alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Seroma Additional description: Abnormal fluid collection in a tissue or organ alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Soft tissue necrosis Additional description: Death of tissue of the belly alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Back pain alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences causally related to treatment / all 1 / 6      deaths causally related to treatment / all 0 / 0 Bone pain alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Chest wall pain alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 1 / 2      deaths causally related to treatment / all 0 / 0 Joint pain alternative assessment type: Non-systematic      subjects affected / exposed 14 / 3297 (0.42%)      occurrences causally related to treatment / all 0 / 15      deaths causally related to treatment / all 0 / 0 Leg pain alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Muscle pain alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 1 / 2      deaths causally related to treatment / all 0 / 0 Infections and infestations Infection - Other alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Infection of body tissue Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Infection of the lung (pneumonia) Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Infection of the skin Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 14 / 3297 (0.42%)      occurrences causally related to treatment / all 0 / 14      deaths causally related to treatment / all 0 / 0 Infection of the stomach Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Infection of the upper respiratory tract Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Infection of the urinary tract Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Large intestine infection Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 Wound infection Additional description: Infection with unknown ANC alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events Full Analysis Set Total subjects affected by non serious adverse events      subjects affected / exposed 1946 / 3297 (59.02%) Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy - possibly related to cancer treatment Additional description: Development of a new cancer resulting from treatment from an earlier cancer diagnosis      subjects affected / exposed 33 / 3297 (1.00%)      occurrences all number 39 Vascular disorders Hematoma Additional description: Blood clot in tissue      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Hemorrhage, CNS Additional description: Bleeding into the brain or spinal cord      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Bleeding of the bladder      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Bleeding of the uterus      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Bleeding of the vagina      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 hemorrhage, pulmonary/upper respiratory      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Dermal change lymphedema, phlebolymphedema      subjects affected / exposed 94 / 3297 (2.85%)      occurrences all number 97 Edema: head and neck Additional description: Swelling of the head and neck area      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Edema: limb Additional description: Swelling of the arms and legs      subjects affected / exposed 146 / 3297 (4.43%)      occurrences all number 156 Edema: trunk/genital Additional description: Swelling of the trunk of the body or genitals      subjects affected / exposed 26 / 3297 (0.79%)      occurrences all number 30 Lymphatics - Other      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Peripheral arterial ischemia Additional description: Disorder of arteries causing inadequate blood supply to extremities.      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Phlebitis (including superficial thrombosis) Additional description: Inflammation of a vein blood clot      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Thrombosis/thrombus/embolism Additional description: Formation or presence of a blood clot inside a blood vessel.      subjects affected / exposed 11 / 3297 (0.33%)      occurrences all number 16 Vascular - Other      subjects affected / exposed 12 / 3297 (0.36%)      occurrences all number 13 Vessel injury-artery Additional description: Damage to a blood vessel in the neck      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Vessel injury-vein Additional description: Damage to a blood vessel that carries blood back from legs      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Surgical and medical procedures Arm intra-operative injury Additional description: Damage to a part of the body during an operation: Arm      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 General disorders and administration site conditions Constitutional Symptoms - Other alternative assessment type: Non-systematic      subjects affected / exposed 14 / 3297 (0.42%)      occurrences all number 14 Fatigue Additional description: asthenia, lethargy, malaise/ fatigue, tiredness, asthenia alternative assessment type: Non-systematic      subjects affected / exposed 340 / 3297 (10.31%)      occurrences all number 351 Fever Additional description: Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) alternative assessment type: Non-systematic      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Rigors/chills Additional description: Chills, shivering alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Sweating (diaphoresis) Additional description: Abnormal sweating alternative assessment type: Non-systematic      subjects affected / exposed 76 / 3297 (2.31%)      occurrences all number 78 Head pain      subjects affected / exposed 100 / 3297 (3.03%)      occurrences all number 102 Pain      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 11 Scalp pain      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Pain - Other      subjects affected / exposed 9 / 3297 (0.27%)      occurrences all number 9 Immune system disorders Allergic reaction Additional description: Allergic reaction/hypersensitivity (including drug fever) alternative assessment type: Non-systematic      subjects affected / exposed 17 / 3297 (0.52%)      occurrences all number 17 Allergic rhinitis Additional description: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip); Stuffy or runny nose, sneezing alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Allergy/Immunology - Other alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 7 Reproductive system and breast disorders Breast pain      subjects affected / exposed 67 / 3297 (2.03%)      occurrences all number 70 Vagina pain      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Breast function/lactation Additional description: Change in ability to produce milk from breasts      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Breast volume/hypoplasia Additional description: Decreased size of breast tissue      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Irregular menses (change from baseline) Additional description: Irregular menstrual periods      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Libido Additional description: Decrease in sexual desire      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 10 Orgasmic dysfunction      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Sexual/Reproductive Function - Other      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Vaginal discharge (non-infectious)      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Vaginal dryness      subjects affected / exposed 45 / 3297 (1.36%)      occurrences all number 46 Vaginal mucositis Additional description: Irritation or sores of the lining of the vagina      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 7 Respiratory, thoracic and mediastinal disorders Pain in the membranes that line the chest cavity and cover the lungs      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Adult Respiratory Distress Syndrome Additional description: Severe life- threatening damage to the lungs which can lead to fluid in the lungs      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Cough      subjects affected / exposed 43 / 3297 (1.30%)      occurrences all number 43 Dyspnea Additional description: Shortness of breath      subjects affected / exposed 82 / 3297 (2.49%)      occurrences all number 84 Hypoxia Additional description: Condition in which there is a decrease in the oxygen supply to a tissue      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Blockage of an air tube from the windpipe to the lungs      subjects affected / exposed 8 / 3297 (0.24%)      occurrences all number 9 Blockage or narrowing in the throat      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Blockage or narrowing of the windpipe      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Pleural effusion (non-malignant) Additional description: Collection of fluid between the thin layers of tissue (pleura) lining the lung and the wall of the chest cavity      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Pneumonitis/pulmonary infiltrates Additional description: Inflammation of the lungs      subjects affected / exposed 14 / 3297 (0.42%)      occurrences all number 16 Pulmonary fibrosis (radiographic changes) Additional description: Scarring of the lungs that can affect your ability to breath and may make you short of breath      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Pulmonary/Upper Respiratory - Other      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Voice changes/dysarthria Additional description: e.g., hoarseness, loss or alteration in voice, laryngitis      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Psychiatric disorders Insomnia Additional description: Difficulty sleeping or falling asleep alternative assessment type: Non-systematic      subjects affected / exposed 251 / 3297 (7.61%)      occurrences all number 259 Memory impairment      subjects affected / exposed 21 / 3297 (0.64%)      occurrences all number 21 Mental status Additional description: Changes in mental status      subjects affected / exposed 21 / 3297 (0.64%)      occurrences all number 21 Agitation      subjects affected / exposed 11 / 3297 (0.33%)      occurrences all number 11 Anxiety      subjects affected / exposed 15 / 3297 (0.45%)      occurrences all number 17 Depression      subjects affected / exposed 135 / 3297 (4.09%)      occurrences all number 140 Personality/behavioral Additional description: Personality changes      subjects affected / exposed 25 / 3297 (0.76%)      occurrences all number 25 Investigations ALT, SGPT (serum glutamic pyruvic transaminase) Additional description: Abnormal liver enzyme level      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 10 Bilirubin (hyperbilirubinemia) Additional description: Abnormal level of bilirubin in the blood. Bilirubin is a bile pigment found in the liver.      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Calcium, serum-low (hypocalcemia) Additional description: Decreased blood calcium level      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Cholesterol, serum-high (hypercholesteremia) Additional description: Increased blood cholesterol level      subjects affected / exposed 27 / 3297 (0.82%)      occurrences all number 27 Creatinine Additional description: Increased blood level of creatinine, a substance normally eliminated by the kidneys into the urine      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 GGT (gamma-Glutamyl transpeptidase) Additional description: Abnormal blood level of liver enzyme      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Glucose, serum-high (hyperglycemia) Additional description: High blood sugar level      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Potassium, serum-low (hypokalemia) Additional description: Decreased blood potassium level      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Uric acid, serum-high (hyperuricemia) Additional description: Increased blood level of uric acid, a waste material from food digestion      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Cardiac disorders Cardiac Arrhythmia - Other alternative assessment type: Non-systematic      subjects affected / exposed 8 / 3297 (0.24%)      occurrences all number 8 Conduction abnormality/atrioventricular heart block Additional description: rregular heart beat alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Palpitations Additional description: Feeling the heart racing 'skipping a beat' pounding alternative assessment type: Non-systematic      subjects affected / exposed 15 / 3297 (0.45%)      occurrences all number 15 Supraventricular and nodal arrhythmia, Fast heart beat alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Supraventricular and nodal arrhythmia; Irregular heart beat alternative assessment type: Non-systematic      subjects affected / exposed 7 / 3297 (0.21%)      occurrences all number 7 Vasovagal episode Additional description: Sudden drop in blood pressure that may cause fainting alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Ventricular arrhythmia Additional description: Irregular heart beat alternative assessment type: Non-systematic      subjects affected / exposed 15 / 3297 (0.45%)      occurrences all number 15 Cardiac General - Other alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Cardiac ischemia/infarction alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 7 Hypertension Additional description: High blood pressure alternative assessment type: Non-systematic      subjects affected / exposed 79 / 3297 (2.40%)      occurrences all number 85 Hypotension Additional description: Low blood pressure alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Left ventricular systolic dysfunction Additional description: Decrease in heart's ability to pump blood alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 7 Restrictive cardiomyopathy Additional description: Decrease in heart's ability to pump blood alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Right ventricular dysfunction (cor pulmonale) Additional description: Decrease in heart's ability to pump blood alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Valvular heart disease Additional description: Abnormal heart valves alternative assessment type: Non-systematic      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 6 Chest pain      subjects affected / exposed 19 / 3297 (0.58%)      occurrences all number 19 Chest wall pain      subjects affected / exposed 16 / 3297 (0.49%)      occurrences all number 16 Nervous system disorders Apnea Additional description: Sudden stopping of breathing      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Arachnoiditis/meningismus/radiculitis Additional description: Inflammation of the linings of the brain      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 CNS cerebrovascular ischemia Additional description: Decrease in blood flow to the brain      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Cognitive disturbance Additional description: Disturbances in thinking patterns      subjects affected / exposed 26 / 3297 (0.79%)      occurrences all number 27 Confusion      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 3 Dizziness      subjects affected / exposed 113 / 3297 (3.43%)      occurrences all number 123 Extrapyramidal/involuntary movement/restlessness Additional description: Restless movements caused by abnormalties in the part of the brain that coordinates movement      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Neurology - Other      subjects affected / exposed 30 / 3297 (0.91%)      occurrences all number 30 Neuropathy: cranial, olfactory Additional description: Abnormal function of the nerve responsible for the sense of smell      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Neuropathy: cranial, motory Additional description: Abnormal function of the nerve that controls facial expression      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Neuropathy: motor Additional description: Weakness or loss of function caused by damage to nerves      subjects affected / exposed 7 / 3297 (0.21%)      occurrences all number 7 Neuropathy: sensory Additional description: Condition of the nervous system that causes numbness, tingling, burning.      subjects affected / exposed 183 / 3297 (5.55%)      occurrences all number 198 Speech impairment (e.g., dysphasia or aphasia) Additional description: Speech problems      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Syncope (fainting)      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Tremor      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Nerve pain      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Blood and lymphatic system disorders Hemoglobin Additional description: Decrease in a part of red blood cells that carries oxygen in the body alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Leukocytes (total WBC) Additional description: Decreased total number of white blood cells alternative assessment type: Non-systematic      subjects affected / exposed 9 / 3297 (0.27%)      occurrences all number 10 Platelets Additional description: Decreased number of blood cells that help to clot blood alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 6 Ear and labyrinth disorders Auditory/Ear - Other alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 3 Tinnitus alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Outer ear pain      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Eye disorders Cataract Additional description: Condition in which the lens of the eye becomes cloudy      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 7 Dry eye syndrome      subjects affected / exposed 14 / 3297 (0.42%)      occurrences all number 14 Glaucoma Additional description: High pressure within the eyeball      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 6 Ocular surface disease Additional description: Damage to the surface of the eye      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Ocular/Visual - Other      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 6 Optic disc edema Additional description: Swelling of the nerve in the back of the eye which is responsible for vision      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Proptosis/enophthalmos Additional description: When the eye sticks out further than normal position sunken eyeball      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Retinal detachment Additional description: Separation of the retina from its connection at the back of the eye      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Retinopathy Additional description: Damage to the eye that decreases vision      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Blurred Vision      subjects affected / exposed 25 / 3297 (0.76%)      occurrences all number 26 Vision-flashing lights/floaters Additional description: Seeing flashing lights or floaters      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Vitreous hemorrhage      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Watery eye (epiphora, tearing)      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Eye pain      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Gastrointestinal disorders Anorexia Additional description: Loss of appetite alternative assessment type: Non-systematic      subjects affected / exposed 9 / 3297 (0.27%)      occurrences all number 9 Ascites (non-malignant) Additional description: Fluid collection in the abdomen alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Colitis Additional description: Inflammation of the colon alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Constipation alternative assessment type: Non-systematic      subjects affected / exposed 27 / 3297 (0.82%)      occurrences all number 28 Dehydration alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Dental: periodontal disease Additional description: Gum disease alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Dental: teeth Additional description: Abnormal teeth      subjects affected / exposed 7 / 3297 (0.21%)      occurrences all number 7 Diarrhoea      subjects affected / exposed 33 / 3297 (1.00%)      occurrences all number 33 Distension/bloating, Abdominal Additional description: Feeling of fullness and tightness in the belly      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Dry mouth Additional description: Dry mouth/salivary gland (xerostomia)      subjects affected / exposed 32 / 3297 (0.97%)      occurrences all number 32 Dysphagia (difficulty swallowing)      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 10 Esophagitis Additional description: Inflammation of the esophagus (the tube that carries food from the mouth to the stomach).      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Fistula, GI Additional description: An abnormal connection between large intestine and another organ      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Flatulence Additional description: Too much gas passed from the rectum      subjects affected / exposed 8 / 3297 (0.24%)      occurrences all number 8 Gastritis (including bile reflux gastritis) Additional description: Inflammation of the lining of the stomach      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Gastrointestinal - Other      subjects affected / exposed 15 / 3297 (0.45%)      occurrences all number 20 Heartburn/dyspepsia      subjects affected / exposed 22 / 3297 (0.67%)      occurrences all number 23 Hemorrhoids      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Mucositis/stomatitis, oral Additional description: Irritation or sores in the lining of the mouth      subjects affected / exposed 17 / 3297 (0.52%)      occurrences all number 17 Mucositis/stomatitis, gastric Additional description: Irritation or sores in the lining of the stomach      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Nausea      subjects affected / exposed 87 / 3297 (2.64%)      occurrences all number 89 Salivary gland changes/saliva Additional description: Changes in saliva      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Taste alteration      subjects affected / exposed 14 / 3297 (0.42%)      occurrences all number 14 Ulcer, intestinal Additional description: Ulcer of small intestine      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Ulcer, gastric Additional description: Ulcer of the stomach      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Vomiting      subjects affected / exposed 13 / 3297 (0.39%)      occurrences all number 14 Bleeding of the mouth      subjects affected / exposed 8 / 3297 (0.24%)      occurrences all number 8 Belly pain      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 10 Mouth pain      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Pelvis pain      subjects affected / exposed 15 / 3297 (0.45%)      occurrences all number 15 Stomach pain      subjects affected / exposed 32 / 3297 (0.97%)      occurrences all number 34 Tooth or gum pain      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Hepatobiliary disorders Cholecystitis Additional description: Inflammation of the gallbladder      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Hepatobiliary/Pancreas - Other      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Pancreas, exocrine enzyme deficiency Additional description: Decrease in enzymes from the pancreas that help digest food      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Pancreatitis Additional description: Inflammation of the pancreas      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Gallbladder pain      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Skin and subcutaneous tissue disorders Atrophy, skin Additional description: Thinning of skin alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Atrophy, subcutaneous fat Additional description: Loss of fat under the skin alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Bruising Additional description: Bruising (in absence of Grade 3 or 4 thrombocytopenia) alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Burn alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Dermatology/Skin - Other alternative assessment type: Non-systematic      subjects affected / exposed 90 / 3297 (2.73%)      occurrences all number 91 Dry skin alternative assessment type: Non-systematic      subjects affected / exposed 44 / 3297 (1.33%)      occurrences all number 45 Flushing Additional description: Sudden reddening of the face and/or neck alternative assessment type: Non-systematic      subjects affected / exposed 14 / 3297 (0.42%)      occurrences all number 14 Hair loss Additional description: Hair loss/alopecia (scalp or body) alternative assessment type: Non-systematic      subjects affected / exposed 191 / 3297 (5.79%)      occurrences all number 193 Hyperpigmentation alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Induration/fibrosis Additional description: skin and subcutaneous tissue; hardening of the skin and connective tissues alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Nail changes alternative assessment type: Non-systematic      subjects affected / exposed 32 / 3297 (0.97%)      occurrences all number 33 Pruritus/itching alternative assessment type: Non-systematic      subjects affected / exposed 37 / 3297 (1.12%)      occurrences all number 37 Rash/desquamation Additional description: Rash flaking or sloughing of skin alternative assessment type: Non-systematic      subjects affected / exposed 51 / 3297 (1.55%)      occurrences all number 49 Rash: acne/acneiform Additional description: Acne pimples alternative assessment type: Non-systematic      subjects affected / exposed 9 / 3297 (0.27%)      occurrences all number 9 Rash: dermatitis associated with radiation Additional description: Redness, flaking or sloughing of skin in the radiation treatment area alternative assessment type: Non-systematic      subjects affected / exposed 60 / 3297 (1.82%)      occurrences all number 62 Rash: hand-foot skin reaction Additional description: Inflammation of the skin on the palms of the hands and soles of the feet alternative assessment type: Non-systematic      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Skin breakdown/decubitus ulcer alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Telangiectasia Additional description: Enlargement of small blood vessels near the surface of the skin, causing redness of the skin or lining of the nose or mouth alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Ulceration Additional description: Irritation or destruction of skin or other body tissues. alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Urticaria (hives, welts, wheals) alternative assessment type: Non-systematic      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Wound complication, non-infectious alternative assessment type: Non-systematic      subjects affected / exposed 13 / 3297 (0.39%)      occurrences all number 15 Skin pain      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Renal and urinary disorders Pain of tube draining bladder      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Cystitis Additional description: Inflammation or infection of the bladder      subjects affected / exposed 46 / 3297 (1.40%)      occurrences all number 51 Incontinence, urinary Additional description: Inability to hold urine in the bladder      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Obstruction, GU Additional description: Blockage of tube between kidney and bladder      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Renal failure Additional description: Kidney failure      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 4 Renal/Genitourinary - Other      subjects affected / exposed 8 / 3297 (0.24%)      occurrences all number 18 Urinary frequency/urgency Additional description: Increased need to urinate      subjects affected / exposed 18 / 3297 (0.55%)      occurrences all number 18 Urine color change      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Endocrine disorders Endocrine - Other alternative assessment type: Non-systematic      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Feminization of male Additional description: The development of female physical characteristics in males alternative assessment type: Non-systematic      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Hot flashes alternative assessment type: Non-systematic      subjects affected / exposed 602 / 3297 (18.26%)      occurrences all number 623 Masculinization of female Additional description: The development of male physical characteristics in females alternative assessment type: Non-systematic      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Pancreatic endocrine: glucose intolerance Additional description: Abnormal control of blood sugar level alternative assessment type: Non-systematic      subjects affected / exposed 15 / 3297 (0.45%)      occurrences all number 15 Thyroid function, high (hyperthyroidism, thyrotoxicosis) Additional description: Abnormally high thyroid function alternative assessment type: Non-systematic      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Thyroid function, low (hypothyroidism) Additional description: Abnormally low thyroid function alternative assessment type: Non-systematic      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 10 Musculoskeletal and connective tissue disorders Arthritis (non-septic) Additional description: Arthritis      subjects affected / exposed 28 / 3297 (0.85%)      occurrences all number 29 Bone: spine-scoliosi Additional description: Abnormal curvature of the spine      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Cervical spine-range of motion Additional description: Stiff neck      subjects affected / exposed 7 / 3297 (0.21%)      occurrences all number 7 Extremity-lower (gait/walking) Additional description: Limp      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Fracture Additional description: A broken bone      subjects affected / exposed 37 / 3297 (1.12%)      occurrences all number 39 Joint-function Additional description: Joint stiffness      subjects affected / exposed 125 / 3297 (3.79%)      occurrences all number 133 Lumbar spine-range of motion Additional description: Stiff lower back      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Muscle weakness, generalized or specific area Additional description: Muscle weakness, generalized or specific area (not due to neuropathy); Muscle weakness of arms      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Muscle weakness of legs Additional description: Muscle weakness, generalized or specific area (not due to neuropathy)      subjects affected / exposed 13 / 3297 (0.39%)      occurrences all number 13 Muscle weakness of the whole body Additional description: Muscle weakness, generalized or specific area (not due to neuropathy)      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Musculoskeletal/Soft Tissue - Other      subjects affected / exposed 97 / 3297 (2.94%)      occurrences all number 104 Osteoporosis Additional description: Bone thinning      subjects affected / exposed 140 / 3297 (4.25%)      occurrences all number 142 Seroma Additional description: Abnormal fluid collection in a tissue or organ      subjects affected / exposed 16 / 3297 (0.49%)      occurrences all number 17 Death of tissue of the arms      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Death of tissue of the chest      subjects affected / exposed 5 / 3297 (0.15%)      occurrences all number 5 Death of tissue of the pelvis Additional description: Soft tissue necrosis      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Back pain      subjects affected / exposed 111 / 3297 (3.37%)      occurrences all number 120 Bone pain      subjects affected / exposed 388 / 3297 (11.77%)      occurrences all number 401 Buttock pain      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Joint pain      subjects affected / exposed 942 / 3297 (28.57%)      occurrences all number 1051 Leg pain      subjects affected / exposed 192 / 3297 (5.82%)      occurrences all number 208 Muscle pain      subjects affected / exposed 211 / 3297 (6.40%)      occurrences all number 219 Neck pain      subjects affected / exposed 7 / 3297 (0.21%)      occurrences all number 7 Infections and infestations Colitis, infectious Additional description: e.g., Clostridium difficile      subjects affected / exposed 4 / 3297 (0.12%)      occurrences all number 4 Infection - Other      subjects affected / exposed 10 / 3297 (0.30%)      occurrences all number 10 Infection of the uterus Additional description: Infection with normal ANC or Grade 1 or 2 neutrophils      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Bladder infection Additional description: Infection with unknown ANC      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Bone infection      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Catheter infection      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection in the throat      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of an air tube from the windpipe to the lungs      subjects affected / exposed 16 / 3297 (0.49%)      occurrences all number 17 Infection of body tissue      subjects affected / exposed 8 / 3297 (0.24%)      occurrences all number 8 Infection of clear front part of the eyeball      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of lining of the inner surface of the eyelid and the eyeball      subjects affected / exposed 2 / 3297 (0.06%)      occurrences all number 2 Infection of lymph node      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the belly      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Infection of the eye      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the joint      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Infection of the kidney      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the lung (pneumonia)      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the muscle      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 2 Infection of the nails      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the outer ear      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the skin      subjects affected / exposed 47 / 3297 (1.43%)      occurrences all number 52 Infection of the small intestine      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the stomach      subjects affected / exposed 7 / 3297 (0.21%)      occurrences all number 8 Infection of the tissue that lines body parts      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Infection of the upper respiratory tract      subjects affected / exposed 16 / 3297 (0.49%)      occurrences all number 17 Infection of the voice box      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Large intestine infection      subjects affected / exposed 6 / 3297 (0.18%)      occurrences all number 6 Tooth infection      subjects affected / exposed 1 / 3297 (0.03%)      occurrences all number 1 Flu-like syndrome Additional description: Flu-type symptoms      subjects affected / exposed 27 / 3297 (0.82%)      occurrences all number 28 Metabolism and nutrition disorders Obesity Additional description: More body fat than normal alternative assessment type: Non-systematic      subjects affected / exposed 3 / 3297 (0.09%)      occurrences all number 3 Weight gain alternative assessment type: Non-systematic      subjects affected / exposed 124 / 3297 (3.76%)      occurrences all number 125 Weight loss alternative assessment type: Non-systematic      subjects affected / exposed 17 / 3297 (0.52%)      occurrences all number 18