Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Celecoxib in Treating Patients With Stage III Colon Cancer Previously Treated With Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01150045

Recruitment Status : Unknown

Verified March 2022 by Alliance for Clinical Trials in Oncology.
Recruitment status was: Active, not recruiting

First Posted : June 24, 2010

Results First Posted : August 6, 2021

Last Update Posted : March 22, 2022

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Alliance for Clinical Trials in Oncology

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Colorectal Cancer
Interventions	Drug: celecoxib Drug: 5-fluorouracil Other: placebo Drug: oxaliplatin Drug: leucovorin
Enrollment	2527

Participant Flow

Recruitment Details
Pre-assignment Details	One patient withdrew from the trial before being randomized and was excluded from any analysis.


Arm/Group Title	Arm A - 12 Cycles of FOLFOX Plus Placebo Daily	Arm B - 12 Cycles of FOLFOX Plus Celecoxib Daily	Arm C - 6 Cycles of FOLFOX Plus Placebo Daily	Arm D - 6 Cycles of FOLFOX Plus Celecoxib Daily
Arm/Group Description	The FOLFOX regimen consisted of eve...	The FOLFOX regimen consisted of eve...	The FOLFOX regimen consisted of eve...	The FOLFOX regimen consisted of eve...
Arm/Group Description	The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. > Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. > Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. > Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. > Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.
Period Title: Overall Study
Started	615	647	646	618
Completed	615	646	646	617
Not Completed	0	1	0	1
Reason Not Completed
Protocol Violation	0	1	0	1

Baseline Characteristics

Arm/Group Title		Arm A - FOLFOX and Placebo (12 Treatments)	Arm B - 12 Cycles of FOLFOX Plus Celecoxib Daily	Arm C - 6 Cycles of FOLFOX Plus Placebo Daily	Arm D - 6 Cycles of FOLFOX Plus Celecoxib Daily	Total
Arm/Group Description		The FOLFOX regimen consisted of eve...	The FOLFOX regimen consisted of eve...	The FOLFOX regimen consisted of eve...	The FOLFOX regimen consisted of eve...	Total of all reporting groups
Arm/Group Description		The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil.> Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil.> Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil.> Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil.> Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	Total of all reporting groups
Overall Number of Baseline Participants		615	646	646	617	2524
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All patients that were randomized and evaluable for the primary endpoint are included in this analysis.
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	615 participants	646 participants	646 participants	617 participants	2524 participants
		61.0 (19.3 to 86.5)	61.9 (21.8 to 88.7)	61.0 (20.5 to 84.4)	61.5 (27.7 to 87.6)	61.3 (19.3 to 88.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	615 participants	646 participants	646 participants	617 participants	2524 participants
	Female	265 43.1%	297 46.0%	296 45.8%	276 44.7%	1134 44.9%
	Male	350 56.9%	349 54.0%	350 54.2%	341 55.3%	1390 55.1%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	615 participants	646 participants	646 participants	617 participants	2524 participants
	Hispanic or Latino	42 6.8%	45 7.0%	55 8.5%	49 7.9%	191 7.6%
	Not Hispanic or Latino	559 90.9%	586 90.7%	571 88.4%	552 89.5%	2268 89.9%
	Unknown or Not Reported	14 2.3%	15 2.3%	20 3.1%	16 2.6%	65 2.6%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	615 participants	646 participants	646 participants	617 participants	2524 participants
	American Indian or Alaska Native	3 0.5%	5 0.8%	3 0.5%	4 0.6%	15 0.6%
	Asian	22 3.6%	32 5.0%	21 3.3%	32 5.2%	107 4.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	4 0.6%	2 0.3%	1 0.2%	7 0.3%
	Black or African American	82 13.3%	88 13.6%	76 11.8%	73 11.8%	319 12.6%
	White	487 79.2%	500 77.4%	522 80.8%	488 79.1%	1997 79.1%
	More than one race	1 0.2%	2 0.3%	3 0.5%	0 0.0%	6 0.2%
	Unknown or Not Reported	20 3.3%	15 2.3%	19 2.9%	19 3.1%	73 2.9%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	615 participants	646 participants	646 participants	617 participants	2524 participants
Canada		57	44	70	61	232
United States		558	602	576	556	2292

Outcome Measures

1.Primary Outcome


Title	Disease-free Survival
Description	Disease-Free Survival (DFS) is defined as the time of randomization un...
Description	Disease-Free Survival (DFS) is defined as the time of randomization until documented progression or death from any cause. The endpoint of this trial is to compare disease-free survival of patients with stage III colon cancer randomized to standard chemotherapy only (FOLFOX; Arm A and Arm C) or standard chemotherapy (FOLFOX) with 3 years of celecoxib 400 mg daily (Arm B and Arm D). The percentage of patients who were alive and disease free after 3 years are reported here. A log-rank test stratified with the stratification factors was used to compare disease-free survival (celecoxib vs placebo)
Time Frame	At 3 years of follow-up

Outcome Measure Data

Analysis Population Description

All patients that were randomized and evaluable were included in this analysis.


Arm/Group Title	FOLFOX and Placebo (Arms A +C)	FOLFOX Plus Celecoxib Daily (Arms B + D)
Arm/Group Description:	Arm A ...	Arm B ...
Arm/Group Description:	Arm A The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity. Arm C The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	Arm B The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity. Arm D The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.
Overall Number of Participants Analyzed	1261	1263
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	73.4 (70.8 to 76.0)	76.3 (73.8 to 78.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOLFOX and Placebo (Arms A +C)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.12
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95% 0.76 to 1.03
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival
Description	Overall Survival (DFS) is defined as the time of randomization until d...
Description	Overall Survival (DFS) is defined as the time of randomization until documented death from any cause. The endpoint is to compare overall survival of patients with stage III colon cancer randomized to standard chemotherapy only (FOLFOX; Arm A and Arm C) or standard chemotherapy (FOLFOX) with 5 years of celecoxib 400 mg daily (Arm B and Arm D). The percentage of patients who were alive after 3 years are reported here.
Time Frame	up to 3 years from registration

Outcome Measure Data

Analysis Population Description

All patients that were randomized and evaluable were included in this analysis.


Arm/Group Title	FOLFOX and Placebo (Arms A +C)	FOLFOX Plus Celecoxib Daily (Arms B + D)
Arm/Group Description:	Arm A ...	Arm B ...
Arm/Group Description:	Arm A The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity. Arm C The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.	Arm B The FOLFOX regimen consisted of every 2 weeks cycles for 12 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity. Arm D The FOLFOX regimen consisted of every 2 weeks cycles for 6 cycles of 2-hour infusions of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2, followed by a bolus infusion of 400-mg/m2 of fluorouracil following by 46-48-hour continuous infusion of 2400-mg/m2 of fluorouracil. Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.
Overall Number of Participants Analyzed	1261	1263
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	81.6 (79.4 to 83.9)	84.3 (82.2 to 86.5)

Adverse Events

Time Frame	Adverse events were collected after every 2-week cycle during treatment (up to 12 cycles or 24 weeks of treatment).
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Arm A - FOLFOX and Placebo (12 Treatments)		Arm B - 12 Cycles of FOLFOX Plus Celecoxib Daily		Arm C - 6 Cycles of FOLFOX Plus Placebo Daily		Arm D - 6 Cycles of FOLFOX Plus Celecoxib Daily
Arm/Group Description	Placebo was dosed at 400 mg orally ...		Celecoxib was dosed at 400 mg orall...		Placebo was dosed at 400 mg orally ...		Celecoxib was dosed at 400 mg orall...
Arm/Group Description	Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.		Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.		Placebo was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Placebo was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.		Celecoxib was dosed at 400 mg orally daily, starting by day 1 of the second treatment of FOLFOX. Celecoxib was administered daily for 3 years from the date of initiation of the first dose or until recurrence of disease or unacceptable toxicity.
All-Cause Mortality
	Arm A - FOLFOX and Placebo (12 Treatments)		Arm B - 12 Cycles of FOLFOX Plus Celecoxib Daily		Arm C - 6 Cycles of FOLFOX Plus Placebo Daily		Arm D - 6 Cycles of FOLFOX Plus Celecoxib Daily
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	10/615 (1.63%)		8/647 (1.24%)		10/646 (1.55%)		9/618 (1.46%)
Serious Adverse Events Serious Adverse Events
	Arm A - FOLFOX and Placebo (12 Treatments)		Arm B - 12 Cycles of FOLFOX Plus Celecoxib Daily		Arm C - 6 Cycles of FOLFOX Plus Placebo Daily		Arm D - 6 Cycles of FOLFOX Plus Celecoxib Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/615 (12.52%)		93/647 (14.37%)		72/646 (11.15%)		78/618 (12.62%)
Blood and lymphatic system disorders
Blood disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Febrile neutropenia ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	2/646 (0.31%)	2	3/618 (0.49%)	4
Hemoglobin decreased ^† 1	3/615 (0.49%)	3	5/647 (0.77%)	5	6/646 (0.93%)	6	6/618 (0.97%)	6
Hemolysis ^† 1	3/615 (0.49%)	4	3/647 (0.46%)	5	2/646 (0.31%)	2	7/618 (1.13%)	7
Spleen disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Cardiac disorders
Arrhythmia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Arrhythmia supraventricular ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Asystole ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Atrial fibrillation ^† 1	2/615 (0.33%)	2	2/647 (0.31%)	2	2/646 (0.31%)	2	2/618 (0.32%)	2
Cardiac disorder ^† 1	0/615 (0.00%)	0	3/647 (0.46%)	3	3/646 (0.46%)	3	2/618 (0.32%)	2
Cardiac pain ^† 1	1/615 (0.16%)	2	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Cardiac valve disease ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Cardiopulmonary arrest ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Conduction disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Left ventricular dysfunction ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Left ventricular failure ^† 1	2/615 (0.33%)	3	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Myocardial ischemia ^† 1	5/615 (0.81%)	5	11/647 (1.70%)	11	9/646 (1.39%)	9	7/618 (1.13%)	7
Palpitations ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Restrictive cardiomyopathy ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Sinus bradycardia ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Sinus tachycardia ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Supraventricular tachycardia ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Ear and labyrinth disorders
Hearing impaired ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Eye disorders
Eye disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Optic nerve disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Vision blurred ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Gastrointestinal disorders
Abdominal distension ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Abdominal pain ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	3/646 (0.46%)	3	8/618 (1.29%)	8
Anal mucositis (clin exam) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Colitis ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Colonic obstruction ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	1/618 (0.16%)	1
Colonic perforation ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Constipation ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	2/646 (0.31%)	2	1/618 (0.16%)	1
Diarrhea ^† 1	27/615 (4.39%)	33	33/647 (5.10%)	35	24/646 (3.72%)	25	12/618 (1.94%)	13
Dry mouth ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Duodenal ulcer ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Dysphagia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Enteritis ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Gastric hemorrhage ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Gastric ulcer ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	3/646 (0.46%)	3	0/618 (0.00%)	0
Gastritis ^† 1	2/615 (0.33%)	2	3/647 (0.46%)	4	4/646 (0.62%)	4	1/618 (0.16%)	1
Gastrointestinal disorder ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	2/646 (0.31%)	2	1/618 (0.16%)	1
Hemorrhoids ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Ileal perforation ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Ileus ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Lower gastrointestinal hemorrhage ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Mucositis oral (clin exam) ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Mucositis oral (funct/sympt) ^† 1	1/615 (0.16%)	2	1/647 (0.15%)	1	1/646 (0.15%)	1	2/618 (0.32%)	2
Nausea ^† 1	23/615 (3.74%)	28	22/647 (3.40%)	24	27/646 (4.18%)	29	20/618 (3.24%)	20
Pancreatic necrosis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Pancreatitis ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Rectal hemorrhage ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Rectal mucositis (clin exam) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Salivary gland disorder ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Small intestinal mucositis (clin exam) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Small intestinal obstruction ^† 1	4/615 (0.65%)	4	1/647 (0.15%)	1	2/646 (0.31%)	2	3/618 (0.49%)	3
Small intestinal perforation ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Upper gastrointestinal hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Vomiting ^† 1	13/615 (2.11%)	15	10/647 (1.55%)	12	17/646 (2.63%)	17	8/618 (1.29%)	8
General disorders
Chest pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Chills ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Death NOS ^† 1	4/615 (0.65%)	4	0/647 (0.00%)	0	0/646 (0.00%)	0	5/618 (0.81%)	5
Edema limbs ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Fatigue ^† 1	41/615 (6.67%)	47	50/647 (7.73%)	56	29/646 (4.49%)	32	30/618 (4.85%)	30
Fever ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	3/646 (0.46%)	3	0/618 (0.00%)	0
Flu-like symptoms ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	2/646 (0.31%)	2	0/618 (0.00%)	0
Gait abnormal ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
General symptom ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Multi-organ failure ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Pain ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Sudden death ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	2/646 (0.31%)	2	1/618 (0.16%)	1
Hepatobiliary disorders
Cholecystitis ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Gallbladder fistula ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Hepatobiliary disease ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Immune system disorders
Hypersensitivity ^† 1	2/615 (0.33%)	2	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Infections and infestations
Abdominal infection ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Bladder infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Bone infection(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Catheter related infection(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Encephalitis infection(unknown ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Gallbladder infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Infection(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Infectious colitis(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Infectious colitis(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Pharyngitis(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Pneumonia(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Pneumonia(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Sepsis(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Sepsis(gr 3/4 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Sepsis(unknown ANC) ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	1/646 (0.15%)	1	1/618 (0.16%)	1
Skin infection ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Soft tissue infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Soft tissue infection(unknown ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Upper respiratory infection(unknown ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Urethral infection(gr 3/4 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Urinary tract infection(gr 3/4 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Wound infection ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Wound infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Injury, poisoning and procedural complications
Aortic injury ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Fracture ^† 1	1/615 (0.16%)	2	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Intestinal stoma obstruction ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Intraoperative breast injury ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Vascular access complication ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	1/618 (0.16%)	1
Investigations
Alanine aminotransferase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Alkaline phosphatase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Amylase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Aspartate aminotransferase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	3/618 (0.49%)	5
Blood bilirubin increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	2/646 (0.31%)	2	1/618 (0.16%)	1
Cardiac troponin I increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Creatinine increased ^† 1	11/615 (1.79%)	13	15/647 (2.32%)	15	11/646 (1.70%)	12	11/618 (1.78%)	11
Electrocardiogram QTc interval prolonged ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
INR increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Laboratory test abnormal ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Leukocyte count decreased ^† 1	3/615 (0.49%)	3	4/647 (0.62%)	4	4/646 (0.62%)	4	2/618 (0.32%)	2
Lipase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Lymphocyte count decreased ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Neutrophil count decreased ^† 1	21/615 (3.41%)	23	26/647 (4.02%)	30	16/646 (2.48%)	18	17/618 (2.75%)	18
Platelet count decreased ^† 1	25/615 (4.07%)	27	36/647 (5.56%)	41	20/646 (3.10%)	21	8/618 (1.29%)	9
Weight gain ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Weight loss ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	2/646 (0.31%)	2	0/618 (0.00%)	0
Metabolism and nutrition disorders
Acidosis ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Anorexia ^† 1	5/615 (0.81%)	7	1/647 (0.15%)	1	2/646 (0.31%)	2	1/618 (0.16%)	1
Blood glucose increased ^† 1	4/615 (0.65%)	4	8/647 (1.24%)	9	5/646 (0.77%)	5	5/618 (0.81%)	5
Dehydration ^† 1	7/615 (1.14%)	9	7/647 (1.08%)	7	6/646 (0.93%)	6	2/618 (0.32%)	2
Glucose intolerance ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Obesity ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Serum albumin decreased ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	3/646 (0.46%)	3	4/618 (0.65%)	4
Serum calcium decreased ^† 1	3/615 (0.49%)	3	0/647 (0.00%)	0	3/646 (0.46%)	3	1/618 (0.16%)	1
Serum glucose decreased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Serum magnesium decreased ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Serum magnesium increased ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Serum phosphate decreased ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	2/646 (0.31%)	2	1/618 (0.16%)	1
Serum potassium decreased ^† 1	5/615 (0.81%)	6	4/647 (0.62%)	4	3/646 (0.46%)	3	4/618 (0.65%)	4
Serum potassium increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	1	1/618 (0.16%)	1
Serum sodium decreased ^† 1	1/615 (0.16%)	1	4/647 (0.62%)	4	1/646 (0.15%)	1	1/618 (0.16%)	1
Serum sodium increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Back pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Bone pain ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Muscle weakness ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Musculoskeletal disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Pain in extremity ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Nervous system disorders
Ataxia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Cognitive disturbance ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Depressed level of consciousness ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Dizziness ^† 1	1/615 (0.16%)	1	3/647 (0.46%)	5	0/646 (0.00%)	0	1/618 (0.16%)	1
Dysgeusia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Headache ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Intracranial hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	2/646 (0.31%)	2	1/618 (0.16%)	1
Ischemia cerebrovascular ^† 1	4/615 (0.65%)	4	0/647 (0.00%)	0	2/646 (0.31%)	2	2/618 (0.32%)	2
Memory impairment ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Neurological disorder NOS ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Peripheral motor neuropathy ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Peripheral sensory neuropathy ^† 1	49/615 (7.97%)	59	54/647 (8.35%)	64	35/646 (5.42%)	38	32/618 (5.18%)	34
Radiculitis brachial ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Syncope ^† 1	1/615 (0.16%)	1	3/647 (0.46%)	3	1/646 (0.15%)	1	1/618 (0.16%)	1
Psychiatric disorders
Agitation ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Anxiety ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Confusion ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	2/618 (0.32%)	2
Depression ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	2/618 (0.32%)	2
Insomnia ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Personality change ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Psychosis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Renal and urinary disorders
Bladder pain ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Glomerular filtration rate decreased ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Renal failure ^† 1	3/615 (0.49%)	3	2/647 (0.31%)	2	1/646 (0.15%)	1	2/618 (0.32%)	2
Urogenital disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Aspiration ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Cough ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	2
Dyspnea ^† 1	3/615 (0.49%)	3	4/647 (0.62%)	4	0/646 (0.00%)	0	1/618 (0.16%)	1
Hiccups ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Hypoxia ^† 1	2/615 (0.33%)	2	3/647 (0.46%)	3	1/646 (0.15%)	1	0/618 (0.00%)	0
Pleural effusion ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Pneumonitis ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Respiratory disorder ^† 1	3/615 (0.49%)	3	4/647 (0.62%)	4	3/646 (0.46%)	3	0/618 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Dry skin ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Hand-and-foot syndrome/reaction ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Nail disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Pain of skin ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Pruritus ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Rash acneiform ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Rash desquamating ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Skin disorder ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Skin hyperpigmentation ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Vascular disorders
Hemorrhage ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Hypertension ^† 1	13/615 (2.11%)	13	17/647 (2.63%)	18	16/646 (2.48%)	18	16/618 (2.59%)	21
Hypotension ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	2/646 (0.31%)	2	1/618 (0.16%)	1
Peripheral ischemia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Phlebitis ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Thrombosis ^† 1	8/615 (1.30%)	8	12/647 (1.85%)	12	8/646 (1.24%)	17	2/618 (0.32%)	2
Vascular disorder ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
1 Term from vocabulary, MedDRA12 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A - FOLFOX and Placebo (12 Treatments)		Arm B - 12 Cycles of FOLFOX Plus Celecoxib Daily		Arm C - 6 Cycles of FOLFOX Plus Placebo Daily		Arm D - 6 Cycles of FOLFOX Plus Celecoxib Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	574/615 (93.33%)		615/647 (95.05%)		618/646 (95.67%)		589/618 (95.31%)
Blood and lymphatic system disorders
Blood disorder ^† 1	1/615 (0.16%)	1	4/647 (0.62%)	27	4/646 (0.62%)	15	3/618 (0.49%)	5
Bone marrow hypocellular ^† 1	1/615 (0.16%)	3	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Febrile neutropenia ^† 1	9/615 (1.46%)	11	12/647 (1.85%)	14	17/646 (2.63%)	18	15/618 (2.43%)	17
Hemoglobin decreased ^† 1	13/615 (2.11%)	33	23/647 (3.55%)	51	10/646 (1.55%)	15	18/618 (2.91%)	21
Hemolysis ^† 1	63/615 (10.24%)	194	53/647 (8.19%)	158	49/646 (7.59%)	102	49/618 (7.93%)	108
Thrombotic microangiopathy ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Cardiac disorders
Arrhythmia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Arrhythmia supraventricular ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Atrial fibrillation ^† 1	2/615 (0.33%)	3	4/647 (0.62%)	4	6/646 (0.93%)	10	0/618 (0.00%)	0
Atrial flutter ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	6	1/646 (0.15%)	4	0/618 (0.00%)	0
Cardiac disorder ^† 1	3/615 (0.49%)	4	2/647 (0.31%)	2	1/646 (0.15%)	1	1/618 (0.16%)	1
Cardiac pain ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	4	0/646 (0.00%)	0	2/618 (0.32%)	2
Cardiac valve disease ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Conduction disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Left ventricular dysfunction ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Left ventricular failure ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Myocardial ischemia ^† 1	3/615 (0.49%)	3	6/647 (0.93%)	7	4/646 (0.62%)	4	4/618 (0.65%)	5
Palpitations ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	7	2/646 (0.31%)	2	2/618 (0.32%)	4
Restrictive cardiomyopathy ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Sinus tachycardia ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Supraventricular tachycardia ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Ventricular tachycardia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Ear and labyrinth disorders
Ear pain ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Hearing impaired ^† 1	3/615 (0.49%)	11	2/647 (0.31%)	20	1/646 (0.15%)	7	1/618 (0.16%)	2
Middle ear inflammation ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Tinnitus ^† 1	1/615 (0.16%)	10	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Endocrine disorders
Endocrine disorder ^† 1	1/615 (0.16%)	6	1/647 (0.15%)	1	2/646 (0.31%)	2	1/618 (0.16%)	1
Hypothyroidism ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Eye disorders
Cataract ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	3/646 (0.46%)	9	1/618 (0.16%)	6
Dry eye syndrome ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	3	1/646 (0.15%)	1	1/618 (0.16%)	1
Eye disorder ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	3	1/646 (0.15%)	3	1/618 (0.16%)	1
Eye pain ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	3	0/618 (0.00%)	0
Optic nerve disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	19	0/618 (0.00%)	0
Optic nerve edema ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Retinal detachment ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	2	0/618 (0.00%)	0
Vision blurred ^† 1	2/615 (0.33%)	2	2/647 (0.31%)	2	4/646 (0.62%)	14	4/618 (0.65%)	10
Vitreous hemorrhage ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Watering eyes ^† 1	4/615 (0.65%)	4	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Gastrointestinal disorders
Abdominal distension ^† 1	3/615 (0.49%)	21	1/647 (0.15%)	1	1/646 (0.15%)	2	1/618 (0.16%)	1
Abdominal pain ^† 1	21/615 (3.41%)	30	21/647 (3.25%)	31	19/646 (2.94%)	26	21/618 (3.40%)	27
Anal pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Cheilitis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Colitis ^† 1	3/615 (0.49%)	3	2/647 (0.31%)	2	1/646 (0.15%)	1	2/618 (0.32%)	2
Colonic hemorrhage ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Colonic obstruction ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	3/618 (0.49%)	4
Colonic perforation ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Colonic ulcer ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Constipation ^† 1	15/615 (2.44%)	24	11/647 (1.70%)	21	25/646 (3.87%)	51	21/618 (3.40%)	43
Diarrhea ^† 1	339/615 (55.12%)	1107	361/647 (55.80%)	1252	353/646 (54.64%)	922	326/618 (52.75%)	857
Dry mouth ^† 1	3/615 (0.49%)	4	3/647 (0.46%)	5	2/646 (0.31%)	8	0/618 (0.00%)	0
Duodenal hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Duodenal obstruction ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Duodenal ulcer ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Dyspepsia ^† 1	5/615 (0.81%)	26	7/647 (1.08%)	9	6/646 (0.93%)	20	7/618 (1.13%)	19
Dysphagia ^† 1	1/615 (0.16%)	2	2/647 (0.31%)	2	1/646 (0.15%)	1	2/618 (0.32%)	2
Enteritis ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Esophageal mucositis (clin exam) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Esophageal mucositis (funct/sympt) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	3/646 (0.46%)	3	0/618 (0.00%)	0
Esophageal pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	3	0/618 (0.00%)	0
Esophagitis ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	1/646 (0.15%)	4	0/618 (0.00%)	0
Fecal incontinence ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	2
Flatulence ^† 1	3/615 (0.49%)	9	1/647 (0.15%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Gastric hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Gastric mucositis (clin exam) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Gastric mucositis (funct/sympt) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Gastric ulcer ^† 1	5/615 (0.81%)	9	13/647 (2.01%)	17	8/646 (1.24%)	9	9/618 (1.46%)	12
Gastritis ^† 1	39/615 (6.34%)	70	40/647 (6.18%)	64	39/646 (6.04%)	63	42/618 (6.80%)	80
Gastrointestinal disorder ^† 1	6/615 (0.98%)	7	8/647 (1.24%)	25	3/646 (0.46%)	4	7/618 (1.13%)	9
Gastrointestinal fistula ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Gastrointestinal pain ^† 1	1/615 (0.16%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Hemorrhoids ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Ileal perforation ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Ileus ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	1/646 (0.15%)	1	3/618 (0.49%)	3
Jejunal obstruction ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Large intestinal mucositis (funct/sympt) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Lower gastrointestinal hemorrhage ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Malabsorption ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Mucositis oral (clin exam) ^† 1	6/615 (0.98%)	6	2/647 (0.31%)	2	2/646 (0.31%)	2	5/618 (0.81%)	5
Mucositis oral (funct/sympt) ^† 1	12/615 (1.95%)	16	17/647 (2.63%)	25	8/646 (1.24%)	11	9/618 (1.46%)	10
Nausea ^† 1	375/615 (60.98%)	1151	395/647 (61.05%)	1240	393/646 (60.84%)	857	360/618 (58.25%)	844
Oral hemorrhage ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Oral pain ^† 1	2/615 (0.33%)	3	2/647 (0.31%)	4	2/646 (0.31%)	3	2/618 (0.32%)	4
Pancreatitis ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Periodontal disease ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Proctitis ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	2
Rectal hemorrhage ^† 1	0/615 (0.00%)	0	3/647 (0.46%)	5	4/646 (0.62%)	5	2/618 (0.32%)	2
Rectal mucositis (clin exam) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Rectal pain ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Salivary gland disorder ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Small intestinal obstruction ^† 1	4/615 (0.65%)	5	4/647 (0.62%)	4	3/646 (0.46%)	4	4/618 (0.65%)	4
Stomach pain ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	1/618 (0.16%)	1
Tooth disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	3	0/646 (0.00%)	0	0/618 (0.00%)	0
Toothache ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Vomiting ^† 1	164/615 (26.67%)	271	167/647 (25.81%)	283	143/646 (22.14%)	204	118/618 (19.09%)	195
General disorders
Chest pain ^† 1	1/615 (0.16%)	3	3/647 (0.46%)	3	3/646 (0.46%)	3	0/618 (0.00%)	0
Chills ^† 1	2/615 (0.33%)	2	1/647 (0.15%)	1	1/646 (0.15%)	2	1/618 (0.16%)	1
Edema limbs ^† 1	8/615 (1.30%)	14	10/647 (1.55%)	38	9/646 (1.39%)	15	7/618 (1.13%)	8
Facial pain ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	3/646 (0.46%)	6	0/618 (0.00%)	0
Fatigue ^† 1	471/615 (76.59%)	2400	500/647 (77.28%)	2649	491/646 (76.01%)	1972	456/618 (73.79%)	1723
Fever ^† 1	5/615 (0.81%)	5	0/647 (0.00%)	0	0/646 (0.00%)	0	3/618 (0.49%)	3
Flu-like symptoms ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	2/646 (0.31%)	4	4/618 (0.65%)	6
Gait abnormal ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	8	0/646 (0.00%)	0	2/618 (0.32%)	2
General symptom ^† 1	1/615 (0.16%)	3	2/647 (0.31%)	3	1/646 (0.15%)	6	2/618 (0.32%)	2
Hypothermia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	2
Ill-defined disorder ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	0/646 (0.00%)	0	2/618 (0.32%)	3
Injection site reaction ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	2/646 (0.31%)	2	0/618 (0.00%)	0
Localized edema ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Pain ^† 1	11/615 (1.79%)	17	12/647 (1.85%)	20	14/646 (2.17%)	22	14/618 (2.27%)	22
Hepatobiliary disorders
Cholecystitis ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	2/646 (0.31%)	2	1/618 (0.16%)	1
Gallbladder pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Hepatobiliary disease ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	9
Immune system disorders
Cytokine release syndrome ^† 1	2/615 (0.33%)	2	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Hypersensitivity ^† 1	12/615 (1.95%)	13	7/647 (1.08%)	8	5/646 (0.77%)	5	7/618 (1.13%)	9
Immune system disorder ^† 1	2/615 (0.33%)	5	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Infections and infestations
Abdominal infection ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Abdominal infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Anorectal infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Bladder infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Bladder infection(gr 3/4 ANC) ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Bladder infection(unknown ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Bone infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Bone infection(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Bronchitis(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Bronchitis(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Catheter related infection ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Catheter related infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Colitis, infectious ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Conjunctivitis ^† 1	2/615 (0.33%)	3	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Device related infection(unknown ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Duodenal infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Endocarditis infective(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Gallbladder infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Infection(gr 0/1/2 ANC) ^† 1	4/615 (0.65%)	4	6/647 (0.93%)	8	4/646 (0.62%)	5	4/618 (0.65%)	4
Infectious colitis(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Infectious colitis(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	1/618 (0.16%)	1
Infectious meningitis(gr 3/4 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Kidney infection(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Kidney infection(gr 3/4 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Laryngitis(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Nail infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	3	0/646 (0.00%)	0	0/618 (0.00%)	0
Otitis media(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Peripheral nerve infection(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Pneumonia(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Pneumonia(gr 3/4 ANC) ^† 1	2/615 (0.33%)	2	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Pneumonia(unknown ANC) ^† 1	3/615 (0.49%)	3	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Rhinitis infective(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Salivary gland infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Scrotal infection(unknown ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	2	0/618 (0.00%)	0
Sepsis(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Sepsis(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Sinusitis(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Sinusitis(gr 3/4 ANC) ^† 1	1/615 (0.16%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Skin infection ^† 1	1/615 (0.16%)	1	4/647 (0.62%)	4	4/646 (0.62%)	5	3/618 (0.49%)	7
Skin infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	2/646 (0.31%)	2	3/618 (0.49%)	3
Skin infection(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Soft tissue infection(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Soft tissue infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Tooth infection ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	3/618 (0.49%)	3
Tooth infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Upper respiratory infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	2/618 (0.32%)	2
Upper respiratory infection(unknown ANC) ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	2/646 (0.31%)	3	1/618 (0.16%)	1
Upper respiratory infectn(gr 0/1/2 ANC) ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Urinary tract infection(gr 0/1/2 ANC) ^† 1	4/615 (0.65%)	4	3/647 (0.46%)	3	1/646 (0.15%)	1	4/618 (0.65%)	4
Urinary tract infection(gr 3/4 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Urinary tract infection(unknown ANC) ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	1/646 (0.15%)	2	3/618 (0.49%)	3
Vaginal infection(gr 0/1/2 ANC) ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Viral hepatitis ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	3	0/646 (0.00%)	0	0/618 (0.00%)	0
Wound infection ^† 1	0/615 (0.00%)	0	4/647 (0.62%)	5	2/646 (0.31%)	3	0/618 (0.00%)	0
Wound infection(gr 0/1/2 ANC) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Wound infection(gr 3/4 ANC) ^† 1	1/615 (0.16%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Injury, poisoning and procedural complications
Arterial injury - Extremity-lower ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Bruising ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Fracture ^† 1	4/615 (0.65%)	5	6/647 (0.93%)	6	3/646 (0.46%)	3	1/618 (0.16%)	1
Injury to carotid artery ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Intraop. inj. - Colon ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Intraop. inj. - Joint ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	2
Intraop. inj. - Small bowel NOS ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Intraop. inj. - Vein-major visceral vein ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Intraoperative complications ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	3	0/646 (0.00%)	0	0/618 (0.00%)	0
Intraoperative gastrointestinal injury ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	5
Intraoperative ocular injury ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	2
Intraoperative urinary injury - Bladder ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Large intestinal anastomotic leak ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Postoperative hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Rectal anastomotic leak ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Vascular access complication ^† 1	4/615 (0.65%)	16	5/647 (0.77%)	5	9/646 (1.39%)	19	5/618 (0.81%)	10
Venous injury - Extremity-lower ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Wound dehiscence ^† 1	2/615 (0.33%)	2	1/647 (0.15%)	7	0/646 (0.00%)	0	3/618 (0.49%)	3
Investigations
Activated partial throm time prolonged ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	2
Alanine aminotransferase increased ^† 1	8/615 (1.30%)	17	10/647 (1.55%)	29	8/646 (1.24%)	12	10/618 (1.62%)	28
Alkaline phosphatase increased ^† 1	8/615 (1.30%)	15	11/647 (1.70%)	19	1/646 (0.15%)	1	5/618 (0.81%)	10
Amylase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Aspartate aminotransferase increased ^† 1	16/615 (2.60%)	35	14/647 (2.16%)	39	8/646 (1.24%)	9	13/618 (2.10%)	28
Blood bilirubin increased ^† 1	4/615 (0.65%)	9	4/647 (0.62%)	6	3/646 (0.46%)	4	4/618 (0.65%)	15
CD4 lymphocytes decreased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	2	0/646 (0.00%)	0	1/618 (0.16%)	1
Creatinine increased ^† 1	76/615 (12.36%)	256	126/647 (19.47%)	418	85/646 (13.16%)	316	100/618 (16.18%)	306
Gamma-glutamyltransferase increased ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	9	0/618 (0.00%)	0
INR increased ^† 1	3/615 (0.49%)	7	8/647 (1.24%)	21	5/646 (0.77%)	10	0/618 (0.00%)	0
Laboratory test abnormal ^† 1	4/615 (0.65%)	8	2/647 (0.31%)	3	0/646 (0.00%)	0	3/618 (0.49%)	4
Leukocyte count decreased ^† 1	23/615 (3.74%)	49	27/647 (4.17%)	43	15/646 (2.32%)	18	18/618 (2.91%)	28
Lipase increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	7	2/646 (0.31%)	4	0/618 (0.00%)	0
Lymphocyte count decreased ^† 1	2/615 (0.33%)	3	6/647 (0.93%)	7	4/646 (0.62%)	4	4/618 (0.65%)	10
Neutrophil count decreased ^† 1	385/615 (62.60%)	987	400/647 (61.82%)	981	303/646 (46.90%)	564	312/618 (50.49%)	583
Platelet count decreased ^† 1	373/615 (60.65%)	1552	417/647 (64.45%)	1827	332/646 (51.39%)	828	315/618 (50.97%)	881
Weight gain ^† 1	10/615 (1.63%)	19	12/647 (1.85%)	33	10/646 (1.55%)	19	8/618 (1.29%)	26
Weight loss ^† 1	9/615 (1.46%)	10	4/647 (0.62%)	5	2/646 (0.31%)	3	4/618 (0.65%)	8
Metabolism and nutrition disorders
Acidosis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	2	1/618 (0.16%)	1
Alkalosis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Anorexia ^† 1	15/615 (2.44%)	28	17/647 (2.63%)	19	8/646 (1.24%)	9	7/618 (1.13%)	18
Blood bicarbonate decreased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	2	0/646 (0.00%)	0	1/618 (0.16%)	1
Blood glucose increased ^† 1	31/615 (5.04%)	74	47/647 (7.26%)	100	37/646 (5.73%)	84	26/618 (4.21%)	55
Blood uric acid increased ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Dehydration ^† 1	4/615 (0.65%)	4	17/647 (2.63%)	24	9/646 (1.39%)	9	6/618 (0.97%)	6
Glucose intolerance ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Obesity ^† 1	1/615 (0.16%)	4	2/647 (0.31%)	12	3/646 (0.46%)	5	3/618 (0.49%)	11
Serum albumin decreased ^† 1	4/615 (0.65%)	9	7/647 (1.08%)	14	5/646 (0.77%)	5	9/618 (1.46%)	15
Serum calcium decreased ^† 1	2/615 (0.33%)	2	3/647 (0.46%)	10	6/646 (0.93%)	10	5/618 (0.81%)	6
Serum calcium increased ^† 1	3/615 (0.49%)	5	4/647 (0.62%)	5	4/646 (0.62%)	6	0/618 (0.00%)	0
Serum glucose decreased ^† 1	1/615 (0.16%)	1	3/647 (0.46%)	3	4/646 (0.62%)	4	2/618 (0.32%)	2
Serum magnesium decreased ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	3	1/646 (0.15%)	1	1/618 (0.16%)	1
Serum phosphate decreased ^† 1	4/615 (0.65%)	8	3/647 (0.46%)	5	4/646 (0.62%)	8	3/618 (0.49%)	3
Serum potassium decreased ^† 1	28/615 (4.55%)	39	26/647 (4.02%)	33	23/646 (3.56%)	28	11/618 (1.78%)	12
Serum potassium increased ^† 1	2/615 (0.33%)	2	3/647 (0.46%)	4	4/646 (0.62%)	4	2/618 (0.32%)	2
Serum sodium decreased ^† 1	8/615 (1.30%)	20	6/647 (0.93%)	14	8/646 (1.24%)	17	5/618 (0.81%)	7
Serum sodium increased ^† 1	2/615 (0.33%)	2	2/647 (0.31%)	2	1/646 (0.15%)	1	0/618 (0.00%)	0
Serum triglycerides increased ^† 1	2/615 (0.33%)	2	1/647 (0.15%)	5	2/646 (0.31%)	3	0/618 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	5/615 (0.81%)	17	6/647 (0.93%)	11	11/646 (1.70%)	22	5/618 (0.81%)	8
Arthritis ^† 1	3/615 (0.49%)	5	2/647 (0.31%)	3	1/646 (0.15%)	1	3/618 (0.49%)	9
Back pain ^† 1	14/615 (2.28%)	32	12/647 (1.85%)	36	11/646 (1.70%)	15	12/618 (1.94%)	31
Bone pain ^† 1	2/615 (0.33%)	4	4/647 (0.62%)	7	2/646 (0.31%)	2	2/618 (0.32%)	3
Chest wall pain ^† 1	2/615 (0.33%)	2	1/647 (0.15%)	1	2/646 (0.31%)	2	0/618 (0.00%)	0
Joint effusion ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Joint range motion decr cervical spine ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Muscle weakness ^† 1	5/615 (0.81%)	6	9/647 (1.39%)	9	1/646 (0.15%)	2	4/618 (0.65%)	4
Muscle weakness lower limb ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	0/646 (0.00%)	0	4/618 (0.65%)	4
Muscle weakness right-sided ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Muscle weakness upper limb ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	2
Musculoskeletal disorder ^† 1	4/615 (0.65%)	6	5/647 (0.77%)	11	5/646 (0.77%)	7	5/618 (0.81%)	24
Myalgia ^† 1	6/615 (0.98%)	19	4/647 (0.62%)	11	4/646 (0.62%)	18	6/618 (0.97%)	7
Neck pain ^† 1	4/615 (0.65%)	9	2/647 (0.31%)	2	2/646 (0.31%)	7	1/618 (0.16%)	1
Osteoporosis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Pain in extremity ^† 1	13/615 (2.11%)	31	9/647 (1.39%)	11	7/646 (1.08%)	7	6/618 (0.97%)	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy ^† 1	3/615 (0.49%)	3	3/647 (0.46%)	3	2/646 (0.31%)	2	0/618 (0.00%)	0
Nervous system disorders
Accessory nerve disorder ^† 1	1/615 (0.16%)	3	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	6
Ataxia ^† 1	3/615 (0.49%)	4	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Cognitive disturbance ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Dizziness ^† 1	6/615 (0.98%)	11	10/647 (1.55%)	12	7/646 (1.08%)	7	5/618 (0.81%)	11
Dysgeusia ^† 1	6/615 (0.98%)	11	10/647 (1.55%)	14	5/646 (0.77%)	10	5/618 (0.81%)	8
Extrapyramidal disorder ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Facial nerve disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Headache ^† 1	14/615 (2.28%)	25	12/647 (1.85%)	18	8/646 (1.24%)	14	14/618 (2.27%)	26
Hydrocephalus ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Intracranial hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	2/646 (0.31%)	2	0/618 (0.00%)	0
Ischemia cerebrovascular ^† 1	7/615 (1.14%)	12	7/647 (1.08%)	7	6/646 (0.93%)	6	2/618 (0.32%)	2
Memory impairment ^† 1	3/615 (0.49%)	5	2/647 (0.31%)	4	0/646 (0.00%)	0	0/618 (0.00%)	0
Neuralgia ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	4	0/646 (0.00%)	0	0/618 (0.00%)	0
Neurological disorder NOS ^† 1	4/615 (0.65%)	11	2/647 (0.31%)	5	2/646 (0.31%)	2	0/618 (0.00%)	0
Olfactory nerve disorder ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Peripheral motor neuropathy ^† 1	1/615 (0.16%)	1	3/647 (0.46%)	6	3/646 (0.46%)	4	0/618 (0.00%)	0
Peripheral sensory neuropathy ^† 1	516/615 (83.90%)	4338	556/647 (85.94%)	4460	501/646 (77.55%)	2756	485/618 (78.48%)	2662
Seizure ^† 1	3/615 (0.49%)	4	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Speech disorder ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	5	1/646 (0.15%)	1	0/618 (0.00%)	0
Syncope ^† 1	9/615 (1.46%)	9	9/647 (1.39%)	10	3/646 (0.46%)	3	9/618 (1.46%)	9
Syncope vasovagal ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Tremor ^† 1	2/615 (0.33%)	3	2/647 (0.31%)	3	0/646 (0.00%)	0	1/618 (0.16%)	1
Psychiatric disorders
Agitation ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Anxiety ^† 1	6/615 (0.98%)	14	10/647 (1.55%)	17	10/646 (1.55%)	18	13/618 (2.10%)	20
Confusion ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Depression ^† 1	5/615 (0.81%)	16	5/647 (0.77%)	8	7/646 (1.08%)	18	7/618 (1.13%)	10
Insomnia ^† 1	8/615 (1.30%)	24	10/647 (1.55%)	19	7/646 (1.08%)	24	12/618 (1.94%)	29
Irritability ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	4	0/646 (0.00%)	0	0/618 (0.00%)	0
Personality change ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Psychosis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Renal and urinary disorders
Bladder hemorrhage ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Bladder obstruction ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Cystitis ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	1/618 (0.16%)	1
Glomerular filtration rate decreased ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	2	1/646 (0.15%)	2	1/618 (0.16%)	1
Hemoglobin urine positive ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Hemorrhage urinary tract ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Kidney pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Proteinuria ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Renal failure ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	2/618 (0.32%)	2
Ureteric obstruction ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	3/646 (0.46%)	3	0/618 (0.00%)	0
Urinary frequency ^† 1	2/615 (0.33%)	3	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Urinary incontinence ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	3/618 (0.49%)	4
Urinary retention ^† 1	1/615 (0.16%)	2	1/647 (0.15%)	1	1/646 (0.15%)	1	0/618 (0.00%)	0
Urogenital disorder ^† 1	1/615 (0.16%)	1	5/647 (0.77%)	5	8/646 (1.24%)	9	2/618 (0.32%)	3
Reproductive system and breast disorders
Breast pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	2
Erectile dysfunction ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	2/646 (0.31%)	3	0/618 (0.00%)	0
Irregular menstruation ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	4	0/646 (0.00%)	0	1/618 (0.16%)	1
Nipple deformity ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Scrotal pain ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Vaginal discharge ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	1/618 (0.16%)	1
Vaginal hemorrhage ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Vaginal inflammation ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Vaginal pain ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^† 1	5/615 (0.81%)	5	1/647 (0.15%)	2	0/646 (0.00%)	0	5/618 (0.81%)	13
Apnea ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	2/618 (0.32%)	2
Aspiration ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Atelectasis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	3
Cough ^† 1	7/615 (1.14%)	7	4/647 (0.62%)	4	5/646 (0.77%)	5	10/618 (1.62%)	18
Dyspnea ^† 1	10/615 (1.63%)	13	10/647 (1.55%)	12	8/646 (1.24%)	19	8/618 (1.29%)	14
Epistaxis ^† 1	2/615 (0.33%)	2	5/647 (0.77%)	6	2/646 (0.31%)	3	6/618 (0.97%)	11
Hiccups ^† 1	0/615 (0.00%)	0	4/647 (0.62%)	5	2/646 (0.31%)	4	0/618 (0.00%)	0
Hypoxia ^† 1	3/615 (0.49%)	3	1/647 (0.15%)	2	2/646 (0.31%)	2	1/618 (0.16%)	1
Laryngeal fistula ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Laryngeal pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Nasal congestion ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Pharyngeal mucositis (clin exam) ^† 1	0/615 (0.00%)	0	3/647 (0.46%)	3	3/646 (0.46%)	4	0/618 (0.00%)	0
Pharyngeal mucositis (funct/sympt) ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Pharyngolaryngeal pain ^† 1	0/615 (0.00%)	0	2/647 (0.31%)	2	0/646 (0.00%)	0	0/618 (0.00%)	0
Pleural effusion ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Pleuritic pain ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Pneumonitis ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	2/646 (0.31%)	2	5/618 (0.81%)	7
Pneumothorax ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Pulmonary fibrosis ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Respiratory disorder ^† 1	2/615 (0.33%)	5	7/647 (1.08%)	8	3/646 (0.46%)	3	2/618 (0.32%)	2
Respiratory tract hemorrhage ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	0/646 (0.00%)	0	1/618 (0.16%)	1
Voice alteration ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	1/646 (0.15%)	1	1/618 (0.16%)	1
Skin and subcutaneous tissue disorders
Alopecia ^† 1	6/615 (0.98%)	14	9/647 (1.39%)	15	6/646 (0.93%)	8	10/618 (1.62%)	17
Dry skin ^† 1	2/615 (0.33%)	2	2/647 (0.31%)	4	2/646 (0.31%)	5	4/618 (0.65%)	10
Erythema multiforme ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Hand-and-foot syndrome/reaction ^† 1	8/615 (1.30%)	13	7/647 (1.08%)	10	3/646 (0.46%)	6	5/618 (0.81%)	6
Nail disorder ^† 1	1/615 (0.16%)	4	2/647 (0.31%)	3	0/646 (0.00%)	0	3/618 (0.49%)	4
Pain of skin ^† 1	1/615 (0.16%)	1	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Pruritus ^† 1	5/615 (0.81%)	6	6/647 (0.93%)	11	2/646 (0.31%)	2	6/618 (0.97%)	11
Rash acneiform ^† 1	1/615 (0.16%)	2	8/647 (1.24%)	13	1/646 (0.15%)	1	3/618 (0.49%)	5
Rash desquamating ^† 1	5/615 (0.81%)	5	4/647 (0.62%)	6	4/646 (0.62%)	8	3/618 (0.49%)	3
Skin disorder ^† 1	6/615 (0.98%)	6	4/647 (0.62%)	4	5/646 (0.77%)	16	6/618 (0.97%)	8
Skin hyperpigmentation ^† 1	3/615 (0.49%)	5	4/647 (0.62%)	9	0/646 (0.00%)	0	3/618 (0.49%)	3
Skin hypopigmentation ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Skin ulceration ^† 1	1/615 (0.16%)	1	0/647 (0.00%)	0	3/646 (0.46%)	3	1/618 (0.16%)	1
Sweating ^† 1	1/615 (0.16%)	2	0/647 (0.00%)	0	1/646 (0.15%)	13	1/618 (0.16%)	8
Urticaria ^† 1	1/615 (0.16%)	1	2/647 (0.31%)	3	2/646 (0.31%)	2	4/618 (0.65%)	4
Vascular disorders
Flushing ^† 1	0/615 (0.00%)	0	1/647 (0.15%)	1	0/646 (0.00%)	0	0/618 (0.00%)	0
Hematoma ^† 1	2/615 (0.33%)	3	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
Hemorrhage ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	2/646 (0.31%)	5	1/618 (0.16%)	1
Hot flashes ^† 1	2/615 (0.33%)	3	5/647 (0.77%)	16	0/646 (0.00%)	0	3/618 (0.49%)	4
Hypertension ^† 1	216/615 (35.12%)	1147	264/647 (40.80%)	1474	250/646 (38.70%)	1159	252/618 (40.78%)	1385
Hypotension ^† 1	4/615 (0.65%)	6	4/647 (0.62%)	6	1/646 (0.15%)	1	3/618 (0.49%)	3
Peripheral ischemia ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	3	0/618 (0.00%)	0
Phlebitis ^† 1	2/615 (0.33%)	2	0/647 (0.00%)	0	0/646 (0.00%)	0	0/618 (0.00%)	0
Thrombosis ^† 1	6/615 (0.98%)	8	17/647 (2.63%)	38	16/646 (2.48%)	24	11/618 (1.78%)	28
Vascular disorder ^† 1	0/615 (0.00%)	0	0/647 (0.00%)	0	1/646 (0.15%)	1	0/618 (0.00%)	0
1 Term from vocabulary, MedDRA12 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Jeffrey A. Meyerhardt, MD, MPH
Organization:	Alliance for Clinical Trials in Oncology
Phone:	617-632-6855
EMail:	jmeyerhardt@partners.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lee S, Ma C, Shi Q, Kumar P, Couture F, Kuebler P, Krishnamurthi S, Lewis D, Tan B, Goldberg RM, Venook A, Blanke C, O'Reilly EM, Shields AF, Meyerhardt JA. Potential Mediators of Oxaliplatin-Induced Peripheral Neuropathy From Adjuvant Therapy in Stage III Colon Cancer: Findings From CALGB (Alliance)/SWOG 80702. J Clin Oncol. 2023 Feb 10;41(5):1079-1091. doi: 10.1200/JCO.22.01637. Epub 2022 Nov 11.

Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.

Meyerhardt JA, Shi Q, Fuchs CS, Meyer J, Niedzwiecki D, Zemla T, Kumthekar P, Guthrie KA, Couture F, Kuebler P, Bendell JC, Kumar P, Lewis D, Tan B, Bertagnolli M, Grothey A, Hochster HS, Goldberg RM, Venook A, Blanke C, O'Reilly EM, Shields AF. Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial. JAMA. 2021 Apr 6;325(13):1277-1286. doi: 10.1001/jama.2021.2454.

Layout table for additonal information

Responsible Party:	Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:	NCT01150045
Other Study ID Numbers:	CALGB-80702 U10CA031946 ( U.S. NIH Grant/Contract ) CALGB-80702 CDR0000675693 ( Registry Identifier: NCI Physician Data Query )
First Submitted:	June 23, 2010
First Posted:	June 24, 2010
Results First Submitted:	May 27, 2021
Results First Posted:	August 6, 2021
Last Update Posted:	March 22, 2022

To Top