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    Clinical Trial Results:
    Phase III trial comparing preoperative chemoradiotherapy with neoadjuvant Folfirinox chemotherapy followed by preoperative chemoradiotherapy for patients with locally advanced rectal cancer (PRODIGE-GERCOR-SFRO-GRECCAR trial).

    Summary
    EudraCT number
    		 2011-004406-25
    Trial protocol
    		 FR  
    Global end of trial date
    01 Jul 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    UC-0110/1005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01804790
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UNICANCER
    Sponsor organisation address
    101 rue de Tolbiac, Paris, France, 75015
    Public contact
    Nourredine AIT-RAHMOUNE, UNICANCER, 33 01 71 93 67 04 , n.a-rahmoune@unicancer.fr
    Scientific contact
    Nourredine AIT-RAHMOUNE, UNICANCER, 33 01 71 93 67 04 , n.a-rahmoune@unicancer.fr
    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
    01 Jul 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jul 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to compare Disease-Free Survival (DFS) after 3 years in the standard preoperative chemotherapy arm versus chemotherapy with Folfirinox followed by standard preoperative chemotherapy arm for patients with locally advanced rectal cancer.
    Protection of trial subjects
    This study was conducted in accordance with the French national regulatory requirements and with: - the European Clinical Trials Directive (2001/20/EC), - the French Huriet law (No. 88-1138) dated 20 December 1988 relative to the protection of individuals taking part in biomedical research and amended by the French Public Health law (No. 2004-806) dated 9 August 2004, - French data protection law No. 78-17 of 6 January 1978 amended by law No. 2004-801 of 6 August 2004 relating to the protection of persons with regard to personal data processing, - French bio-ethics law No. 2004-800 dated 6 August 2004. - Good Clinical Practices dated 24 November 2006.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Jun 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 7 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 461
    Worldwide total number of subjects
    461
    EEA total number of subjects
    461
    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)
    310
    From 65 to 84 years
    151
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 461 subjects were included from 05/06/2012 to 26/06/2017 by 35 participating centers (Only in France).

    Pre-assignment
    Screening details
    		 Patients with histologically confirmed rectal adenocarcinoma <15 cm from the anal verge and MRI-staged T3 at risk of local recurrence or cT4, N-any, M0 were included.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A
    Arm description
    		 Patients included in this arm received: 1) Chemoradiotherapy (CRT) = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 2) Total Mesorectal Excision (TME) Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 3) Adjuvant Chemotherapy (adjuvant CT) = either FOLFOX6 or Capecitabine for 6 months
    Arm type
    		 Standart arm

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Arm B
    Arm description
    		 Patients included in this arm received: 1- Neoadjuvant chemotherapy (mFolfirinox) for 2 months (6 cycles) = Oxaliplatin (85 mg/m2) + Irinotecan (180 mg/m2) + Folinic acid (400 mg/m2) + continuous infusion Fluorouracil (2400 mg/m2) 2- CRT = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 3- TME Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 4- Adjuvant CT = either FOLFOX6 or Capecitabine for 3 months
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oxaliplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received 85g/m² D1 over 2 hours.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients were received 180 mg/m² D1 over 90 minutes starting 30 minutes after the start of folinic acid

    Investigational medicinal product name
    Folinic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients were received 400 mg/m² D1 as a 2-hour infusion.

    Investigational medicinal product name
    5-Fluorouracil (5FU)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients were received 2.4 g/m² as a continuous infusion over 46 hours (1,200 mg/m²/ day).

    Number of subjects in period 1
    		Arm A Arm B
    Started
    230
    231
    Completed
    122
    139
    Not completed
    108
    92
         Physician decision
    32
    30
         Consent withdrawn by subject
    11
    10
         Lost of follow-up
    2
    -
         Toxicity
    13
    22
         Protocol violation
    1
    1
         Death
    8
    3
         Other
    9
    2
         Progression
    22
    7
         Non compliance
    2
    5
         Post surgery complication
    8
    9
         Second cancer
    -
    1
         Metastasis at inclusion
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients included in this arm received: 1) Chemoradiotherapy (CRT) = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 2) Total Mesorectal Excision (TME) Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 3) Adjuvant Chemotherapy (adjuvant CT) = either FOLFOX6 or Capecitabine for 6 months

    Reporting group title
    Arm B
    Reporting group description
    		 Patients included in this arm received: 1- Neoadjuvant chemotherapy (mFolfirinox) for 2 months (6 cycles) = Oxaliplatin (85 mg/m2) + Irinotecan (180 mg/m2) + Folinic acid (400 mg/m2) + continuous infusion Fluorouracil (2400 mg/m2) 2- CRT = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 3- TME Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 4- Adjuvant CT = either FOLFOX6 or Capecitabine for 3 months

    Reporting group values
    		 Arm A Arm B Total
    Number of subjects
    		 230 231 461
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 150 160 310
        From 65-84 years
    		 80 71 151
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 62 (26 to 75) 61 (34 to 77) -
    Gender categorical
    Units: Subjects
        Female
    		 74 81 155
        Male
    		 156 150 306
    WHO
    Units: Subjects
        WHO 0
    		 182 178 360
        WHO 1
    		 44 51 95
        Missing
    		 4 2 6
    Distance from the anal verge (TenAlea Data)
    Units: Subjects
        ≤5cm
    		 94 93 187
        5.1-10cm
    		 113 114 227
        10.1-15cm
    		 23 24 47
    cN stage
    Units: Subjects
        N0
    		 26 21 47
        N+
    		 194 200 394
        NX
    		 5 8 13
        Missing
    		 5 2 7
    PI-MA: Anal verge distance to inferior edge of the tumour
    Units: mm
        arithmetic mean (standard deviation)
    		 54.55 ( 25.57 ) 49.51 ( 26.51 ) -
    PI-SA: Distance between the lower pole of the tumour and the anal sphincter
    Units: mm
        median (standard deviation)
    		 28.03 ( 20.01 ) 30.05 ( 27.25 ) -

    End points

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    End points reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients included in this arm received: 1) Chemoradiotherapy (CRT) = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 2) Total Mesorectal Excision (TME) Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 3) Adjuvant Chemotherapy (adjuvant CT) = either FOLFOX6 or Capecitabine for 6 months

    Reporting group title
    Arm B
    Reporting group description
    		 Patients included in this arm received: 1- Neoadjuvant chemotherapy (mFolfirinox) for 2 months (6 cycles) = Oxaliplatin (85 mg/m2) + Irinotecan (180 mg/m2) + Folinic acid (400 mg/m2) + continuous infusion Fluorouracil (2400 mg/m2) 2- CRT = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 3- TME Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 4- Adjuvant CT = either FOLFOX6 or Capecitabine for 3 months

    Primary: Disease-Free Survival (DFS) at 3 years

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    End point title
    		 Disease-Free Survival (DFS) at 3 years
    End point description
    DFS was defined as the time from randomization until the occurrence of the first oncological event, such as local or metastatic recurrence, the development of a second cancer or death, irrespective of cause. Patients without events at the time of the analysis were censored at the date of the last informational follow-up. Locoregional recurrence was defined as an anastomotic recurrence or a local recurrence in the sacral concavity.
    End point type
    Primary
    End point timeframe
    at 3 years
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    230
    231
    Units: percent
        number (confidence interval 95%)
    68.5 (61.9 to 74.2)
    75.7 (69.4 to 80.8)
    Statistical analysis title
    		 DFS analysis
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    461
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34
    Method
    		 Cox proportional-hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 0.97

    Secondary: Overall survival (OS)

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    End point title
    		 Overall survival (OS)
    End point description
    Overall survival (OS) is defined as the interval between the randomization and the occurrence of death whatever the cause. Patients alive at the time of the analysis will be censored on the date of the last informative follow-up.
    End point type
    Secondary
    End point timeframe
    At 7 years.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    230
    231
    Units: percent
        number (confidence interval 95%)
    80 (74.1 to 84.6)
    86.9 (81.6 to 90.7)
    Statistical analysis title
    		 OS analysis
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    461
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.08
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.09

    Secondary: Specific Survival (SS)

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    End point title
    		 Specific Survival (SS)
    End point description
    Specific Survival (SS) was defined as the period between the date of randomization and the date of death due to cancer or to treatment-related toxicity.
    End point type
    Secondary
    End point timeframe
    At 5 years.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    230
    231
    Units: percent
        number (confidence interval 95%)
    82.4 (76.7 to 86.8)
    88.1 (83.1 to 91.8)
    Statistical analysis title
    		 SS analysis
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    461
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.07
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.05

    Secondary: Metastasis-free Survival (MFS)

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    End point title
    		 Metastasis-free Survival (MFS)
    End point description
    Metastasis-Free Survival (MFS) was defined as the period between the randomization and the occurrence of the first distant event at all sites of recurrence distant from the resection site (e.g. peritoneal, hepatic, pulmonary or lymph nodes). Locoregional events were ignored and patients alive without metastasis at the time of analysis were censored on the date of the last exam not having revealed this type of event. Metastatic recurrence rate was deduced from metastasis-free survival.
    End point type
    Secondary
    End point timeframe
    At 5 years.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    230
    231
    Units: Percent
        number (confidence interval 95%)
    67.7 (61.2 to 73.4)
    77.6 (71.5 to 82.5)
    Statistical analysis title
    		 MFS analysis
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    461
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.07
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.02

    Secondary: Local recurrence rate

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    End point title
    		 Local recurrence rate
    End point description
    Local recurrence rate was defined as the rate of anastomotic or local recurrence in the sacral concavity.
    End point type
    Secondary
    End point timeframe
    At 5 years.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    230
    231
    Units: percent
        number (confidence interval 95%)
    6.4 (3.8 to 10.8)
    4.7 (2.5 to 8.5)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were recorded from the date the patient signed the consent form until 28 days after administration of the last dose of product (90 days in the case of radiotherapy).
    Adverse event reporting additional description
    For non serious adverse events only the main toxicities reported during chemoradiotherapy (CRT) were available. The number of occurrence are not available and will be always noted "1"
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.0
    Reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients included in this arm received: 1- Chemoradiotherapy (CRT) = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 2- Total Mesorectal Excision (TME) Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 3- Adjuvant Chemotherapy (adjuvant CT) = either FOLFOX6 or Capecitabine for 6 months

    Reporting group title
    Arm B
    Reporting group description
    		 Patients included in this arm received: 1- Neoadjuvant chemotherapy (mFolfirinox) for 2 months (6 cycles) = Oxaliplatin (85 mg/m2) + Irinotecan (180 mg/m2) + Folinic acid (400 mg/m2) + continuous infusion Fluorouracil (2400 mg/m2) 2- CRT = Radiotherapy + Chemotherapy (50 Gy + Capecitabine; 25 fractions) for 5 weeks 3- TME Surgery (or Partial Mesorectal Excision (PME) for tumours of the upper third) 6 to 8 weeks after CRT 4- Adjuvant CT = either FOLFOX6 or Capecitabine for 3 months

    Serious adverse events
    		 Arm A Arm B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    88 / 230 (38.26%)
    107 / 231 (46.32%)
         number of deaths (all causes)
    56
    42
         number of deaths resulting from adverse events
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma endometrial
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carcinoma vocal cord
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney cancer
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic neuroendocrine tumor
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary metastases
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urothelial carcinoma
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma of the hypopharynx
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cholecystectomy
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteral nutrition
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileostomy closure
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess drainage
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Catheter related thrombosis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 230 (0.00%)
    3 / 231 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fever
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Prolapse
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reaction febrile
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic pain
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Unknown cause of death
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug allergy
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hypertrophy
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fluid collection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal pain
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal hemorrhage
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chest pain
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism pulmonary
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumopathy
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 230 (0.00%)
    3 / 231 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic fistula
         subjects affected / exposed
    4 / 230 (1.74%)
    5 / 231 (2.16%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic leak
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic stenosis
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal stoma necrosis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrostomy failure
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peristomal abscess NOS
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative complication
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Postoperative hernia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound breakdown
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prolapse of intestinal stoma
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture rupture
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trauma
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    2 / 230 (0.87%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute pericarditis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation paroxysmal
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cardio-respiratory failure
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain - cardiac
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary spasm
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary spastic angina
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death sudden
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Myocardial infarct
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tamponade cardiac
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cholinergic syndrome
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epileptic fit
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological disorder
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraplegia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sensory neuropathy
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    0 / 230 (0.00%)
    4 / 231 (1.73%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile aplasia
         subjects affected / exposed
    0 / 230 (0.00%)
    3 / 231 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 230 (0.87%)
    6 / 231 (2.60%)
         occurrences causally related to treatment / all
    2 / 2
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal abscess
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess intestinal
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess perianal
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute pancreatitis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal lesion
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal pain
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bowel obstruction
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic fistula
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic obstruction
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhea
         subjects affected / exposed
    5 / 230 (2.17%)
    5 / 231 (2.16%)
         occurrences causally related to treatment / all
    6 / 6
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhea hemorrhagic
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epigastric pain
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fecal vomiting
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fistula of small intestine
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastro-intestinal disorder NOS
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoperitoneum
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernial eventration
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileitis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    4 / 230 (1.74%)
    5 / 231 (2.16%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction small intestine
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fluid collection
         subjects affected / exposed
    4 / 230 (1.74%)
    3 / 231 (1.30%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal bleeding
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectorrhagia
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectovaginal fistula
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    4 / 230 (1.74%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestine perforation
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subocclusive syndrome
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 230 (0.87%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic pain
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Eczematous rash
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute renal failure
         subjects affected / exposed
    6 / 230 (2.61%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute renal insufficiency
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Functional renal failure
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal insufficiency
         subjects affected / exposed
    3 / 230 (1.30%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Diabetes
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain legs
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess perianal
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia coli infection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pneumonitis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    0 / 230 (0.00%)
    4 / 231 (1.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peritonitis perforative
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumococcal pneumonia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 230 (1.30%)
    5 / 231 (2.16%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septicemia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Septicemia due to Escherichia coli (E. coli)
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin & subcutaneous tissue abscess
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary infection
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    3 / 230 (1.30%)
    0 / 231 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalemia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcemia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalemia
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 231 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 231 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Arm A Arm B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    230 / 230 (100.00%)
    231 / 231 (100.00%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    17 / 230 (7.39%)
    39 / 231 (16.88%)
         occurrences all number
    1
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    13 / 230 (5.65%)
    44 / 231 (19.05%)
         occurrences all number
    1
    1
    Alkaline phosphatase increased
         subjects affected / exposed
    8 / 230 (3.48%)
    33 / 231 (14.29%)
         occurrences all number
    1
    1
    GGT increased
         subjects affected / exposed
    10 / 230 (4.35%)
    67 / 231 (29.00%)
         occurrences all number
    1
    1
    Vascular disorders
    Thromboembolic event
         subjects affected / exposed
    2 / 230 (0.87%)
    2 / 231 (0.87%)
         occurrences all number
    1
    1
    Nervous system disorders
    Peripheral sensory neuropathy
         subjects affected / exposed
    3 / 230 (1.30%)
    30 / 231 (12.99%)
         occurrences all number
    1
    1
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    83 / 230 (36.09%)
    148 / 231 (64.07%)
         occurrences all number
    1
    1
    Neutropenia
         subjects affected / exposed
    30 / 230 (13.04%)
    75 / 231 (32.47%)
         occurrences all number
    1
    1
    Thrombopenia
         subjects affected / exposed
    36 / 230 (15.65%)
    81 / 231 (35.06%)
         occurrences all number
    1
    1
    Lymphopenia
         subjects affected / exposed
    182 / 230 (79.13%)
    182 / 231 (78.79%)
         occurrences all number
    1
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    87 / 230 (37.83%)
    79 / 231 (34.20%)
         occurrences all number
    1
    1
    Fever
         subjects affected / exposed
    3 / 230 (1.30%)
    1 / 231 (0.43%)
         occurrences all number
    1
    1
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    128 / 230 (55.65%)
    127 / 231 (54.98%)
         occurrences all number
    1
    1
    Constipation
         subjects affected / exposed
    39 / 230 (16.96%)
    25 / 231 (10.82%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    44 / 230 (19.13%)
    43 / 231 (18.61%)
         occurrences all number
    1
    1
    Vomiting
         subjects affected / exposed
    10 / 230 (4.35%)
    10 / 231 (4.33%)
         occurrences all number
    1
    1
    Abdominal pain
         subjects affected / exposed
    23 / 230 (10.00%)
    15 / 231 (6.49%)
         occurrences all number
    1
    1
    Anorexia
         subjects affected / exposed
    15 / 230 (6.52%)
    12 / 231 (5.19%)
         occurrences all number
    1
    1
    Stomatitis
         subjects affected / exposed
    8 / 230 (3.48%)
    6 / 231 (2.60%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    2 / 230 (0.87%)
    12 / 231 (5.19%)
         occurrences all number
    1
    1
    Palmar-plantar erythrodysesthesia syndrome
         subjects affected / exposed
    12 / 230 (5.22%)
    15 / 231 (6.49%)
         occurrences all number
    1
    1
    Metabolism and nutrition disorders
    Weight loss
         subjects affected / exposed
    16 / 230 (6.96%)
    9 / 231 (3.90%)
         occurrences all number
    1
    1
    Hyperglycemia
         subjects affected / exposed
    12 / 230 (5.22%)
    10 / 231 (4.33%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Jun 2012
    - Correction of typographical errors on pages 6, 13 page 45 found in the protocol V2 from 26-Apr-2012. - Modification of the investigators list
    12 Dec 2012
    - Correction of typographical errors found in the protocol V3 from 26-Apr-2012 - Modifications of summary table of investigations (H) in the protocol V3 from 26-Apr-2012 - Withdrawal of Annex 7 “Tumours evaluation classification” and modification of the numbers of the following annexes - Modification of the website address used for the randomization process (https://prod.tenalea.net/gso/dm/) - Main objective was disease-free survival not the evaluation of the tumour response according to RECIST (page 45) - The data owner was corrected - Correction of the study title - Modification of the investigators list
    06 Jun 2013
    - Modification of the investigators list
    05 Sep 2013
    - The investigators list was modified
    22 Oct 2013
    - The cardiac assessment to be performed on inclusion before starting treatment to prevent the occurrence of a serious cardiac event under Fluorouracil was detailed - The collection of the quality of life questionnaires became mandatory - Clarification regarding radiotherapy - Homogeneization of the tummary table of investigations and examinations required in the protocol - Update of the contacts list - Modification of the investigators list
    22 Oct 2013
    - The cardiac assessment to be performed on inclusion before starting treatment to prevent the occurrence of a serious cardiac event under Fluorouracil was detailed - The collection of the quality of life questionnaires became mandatory - Clarification regarding radiotherapy - Homogeneization of the tummary table of investigations and examinations required in the protocol - Update of the contacts list - Modification of the investigators list
    03 Feb 2015
    - Inclusion period were extended - An assessment at the end of adjuvant chemotherapy was added (14 days after last adjuvant chemo cyle) - Withdrawal of the recommendation on the use of Calium Gluconate and Magnesium Sulfate to prevent neurotoxicity in patients receiving Oxaliplatin - Clarification of the protocol following the request of participating centres - Update of the contacts list - Modification of the investigators list
    28 May 2015
    - Addition of a new biological study regarding the role of circulating miRNA as predictive biomarker in rectal cancers. - Update of the sampling and storage procedures for biological samples - Update of the contacts list - Modification of the investigators list
    03 Dec 2015
    - Modification of the investigators list
    04 Jan 2017
    - Modification of the coordinator of the study and addition of co-coordinators. - Modification of the investigator list
    03 Jan 2020
    - Modification of the coordinator of the study

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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