Trial Outcomes & Findings for A Safety and Efficacy Study in Patients With Gastric Cancer (NCT NCT00400179)

NCT ID: NCT00400179

Last Updated: 2024-09-19

Results Overview

Survival was defined as the time from the date of randomization to the time of death (from any cause) for each patient.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1053 participants

Primary outcome timeframe

The cutoff date for survival analysis was 07 March 2008 (12 months after last patient randomized).

Results posted on

2024-09-19

Participant Flow

This multicenter study was conducted between May 18, 2005 and March 7, 2008 in 24 countries including the United States. Study centers were also located in Canada, Eastern and Western Europe, South America, Australia, and ex-Soviet Union block of nations.

Participant milestones

Participant milestones
Measure	S-1/Cisplatin In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Overall Study STARTED	527	526
Overall Study COMPLETED	521	508
Overall Study NOT COMPLETED	6	18

Reasons for withdrawal

Reasons for withdrawal
Measure	S-1/Cisplatin In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Overall Study Adverse Event	2	2
Overall Study Death	1	2
Overall Study Withdrew Consent	1	5
Overall Study Disease progression	1	1
Overall Study Intercurrent illness	0	1
Overall Study Investigator judgment	0	1
Overall Study Randomization error/patient ineligible	1	6

Baseline Characteristics

A Safety and Efficacy Study in Patients With Gastric Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	S-1/Cisplatin n=521 Participants In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=508 Participants In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.	Total n=1029 Participants Total of all reporting groups
Age, Continuous Baseline Measure Data (descriptive stats, median)	59.0 Years n=5 Participants	59.0 Years n=7 Participants	59.0 Years n=5 Participants
Sex: Female, Male Female	139 Participants n=5 Participants	161 Participants n=7 Participants	300 Participants n=5 Participants
Sex: Female, Male Male	382 Participants n=5 Participants	347 Participants n=7 Participants	729 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	447 Participants n=5 Participants	438 Participants n=7 Participants	885 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	61 Participants n=5 Participants	53 Participants n=7 Participants	114 Participants n=5 Participants
Body surface area (BSA) Categories </=1.29 m2	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Body surface area (BSA) Categories 1.30-1.49 m2	46 Participants n=5 Participants	44 Participants n=7 Participants	90 Participants n=5 Participants
Body surface area (BSA) Categories 1.50-1.69 m2	118 Participants n=5 Participants	147 Participants n=7 Participants	265 Participants n=5 Participants
Body surface area (BSA) Categories 1.70-1.89 m2	208 Participants n=5 Participants	181 Participants n=7 Participants	389 Participants n=5 Participants
Body surface area (BSA) Categories 1.90-2.09 m2	114 Participants n=5 Participants	93 Participants n=7 Participants	207 Participants n=5 Participants
Body surface area (BSA) Categories 2.10-2.29 m2	29 Participants n=5 Participants	34 Participants n=7 Participants	63 Participants n=5 Participants
Body surface area (BSA) Categories >/=2.30 m2	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	226 Participants n=5 Participants	200 Participants n=7 Participants	426 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	295 Participants n=5 Participants	308 Participants n=7 Participants	603 Participants n=5 Participants
Tissue Type Papillary adenocarcinoma	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Tissue Type Tubular adenocarcinoma	132 Participants n=5 Participants	113 Participants n=7 Participants	245 Participants n=5 Participants
Tissue Type Well-differentiated	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Tissue Type Moderately-differentiated	105 Participants n=5 Participants	91 Participants n=7 Participants	196 Participants n=5 Participants
Tissue Type Unknown	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Tissue Type Poorly differentiated adenocarcinoma	210 Participants n=5 Participants	189 Participants n=7 Participants	399 Participants n=5 Participants
Tissue Type Signet-ring cell carcinoma	75 Participants n=5 Participants	95 Participants n=7 Participants	170 Participants n=5 Participants
Tissue Type Mucinous adenocarcinoma	28 Participants n=5 Participants	32 Participants n=7 Participants	60 Participants n=5 Participants
Tissue Type Other	97 Participants n=5 Participants	94 Participants n=7 Participants	191 Participants n=5 Participants
Tissue Type Adenocarcinoma NOS	87 Participants n=5 Participants	87 Participants n=7 Participants	174 Participants n=5 Participants
Tissue Type Poorly differentiated cancer	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Tissue Type Unknown/not specified	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Tissue Type Other types	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Anatomical Location of Primary Lesion Stomach	438 Participants n=5 Participants	417 Participants n=7 Participants	855 Participants n=5 Participants
Anatomical Location of Primary Lesion Gastroesophageal junction	82 Participants n=5 Participants	88 Participants n=7 Participants	170 Participants n=5 Participants
Anatomical Location of Primary Lesion Stomach and gastroesophageal junction	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Extent of Disease Locally advanced	23 Participants n=5 Participants	20 Participants n=7 Participants	43 Participants n=5 Participants
Extent of Disease 1 metastatic site	157 Participants n=5 Participants	161 Participants n=7 Participants	318 Participants n=5 Participants
Extent of Disease >/=2 metastatic sites	340 Participants n=5 Participants	327 Participants n=7 Participants	667 Participants n=5 Participants
Extent of Disease Not assessed	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Disease Measurability Measureable disease	499 Participants n=5 Participants	485 Participants n=7 Participants	984 Participants n=5 Participants
Disease Measurability Non-measurable disease	21 Participants n=5 Participants	22 Participants n=7 Participants	43 Participants n=5 Participants
Disease Measurability Nonevaluable disease	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Disease Measurability No disease present	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: The cutoff date for survival analysis was 07 March 2008 (12 months after last patient randomized).

Survival was defined as the time from the date of randomization to the time of death (from any cause) for each patient.

Outcome measures

Outcome measures
Measure	S-1/Cisplatin n=521 Participants In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=508 Participants In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Median Survival	8.6 Months Interval 7.9 to 9.5	7.9 Months Interval 7.2 to 8.5

SECONDARY outcome

Timeframe: Data cutoff was 07 March 2008 (12 months after last patient randomized).

The proportion of patients with objective evidence of complete response (CR) or partial response (PR) based on tumor response assessments. Per the Response Evaluation Criteria in Solid tumors (RECIST), CR was defined as the disappearance of all target lesions for at least 4 weeks, and PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	S-1/Cisplatin n=402 Participants In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=385 Participants In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Overall Response Rate (ORR)	29.1 Percentage of patients in each group Interval 24.7 to 33.8	31.9 Percentage of patients in each group Interval 27.3 to 36.9

SECONDARY outcome

Timeframe: Data cutoff was 07 March 2008 (12 months after last patient was randomized).

Duration of response was defined as the time from date of first confirmed response (CR or PR) to date of first progressive disease (PD) or death. Per the RECIST criteria, definitions were as follows: CR was the disappearance of all target lesions for at least 4 weeks, PR was at least a 30% decrease in the sum of the longest diameter of target lesions, and PD was at least a 20% increase in the sum of the longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	S-1/Cisplatin n=402 Participants In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=385 Participants In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Duration of Response (DR)	6.5 Months Interval 5.8 to 7.4	5.8 Months Interval 5.5 to 6.1

SECONDARY outcome

Timeframe: From date of randomization until date of first documented PD, date of death, or until data cutoff on 07 March 2008 (12 months after last patient randomized), whichever came first.

The time from randomization to date of first documented PD or date of death, whichever occurred first.

Outcome measures

Outcome measures
Measure	S-1/Cisplatin n=521 Participants In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=508 Participants In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Progression-free Survival (PFS)	4.8 Months Interval 4.0 to 5.5	5.5 Months Interval 4.4 to 5.8

SECONDARY outcome

Timeframe: From date of randomization until date of permanent discontinuation of S-1 or 5-FU, first documented PD, death, or data cutoff on 07 March 2008 (12 months after last patient randomized), whichever came first.

The time from randomization to date of permanent discontinuation of S-1 or 5-FU, first documented PD, or death, whichever occurred first.

Outcome measures

Outcome measures
Measure	S-1/Cisplatin n=521 Participants In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=508 Participants In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Time to Treatment Failure (TTF)	3.8 Months Interval 3.7 to 4.0	3.8 Months Interval 3.7 to 4.4

Adverse Events

S-1/Cisplatin

Serious events: 257 serious events

Other events: 514 other events

Deaths: 0 deaths

5-FU/Cisplatin

Serious events: 248 serious events

Other events: 504 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Taiho

Taiho Pharma USA, Inc.

Phone: +1 844-878-2446

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Taiho agreements vary with individual investigators, but do not prohibit any from publishing. Taiho is provided time to review material discussing trial results (generally 30 to 120 days with possible extension), and can remove undisclosed confidential, proprietary and intellectual property rights-related information. Authors have final control and approval of publication content of final study results. The investigator agrees not to publish any results before the first multicenter publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	S-1/Cisplatin n=521 participants at risk In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=508 participants at risk In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Blood and lymphatic system disorders Anaemia	6.3% 33/521 • Number of events 37 • From the start of study drug administration until 12 months after last patient randomized	6.1% 31/508 • Number of events 38 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Anaemia megaloblastic	0.19% 1/521 • Number of events 2 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Bone marrow failure	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Febrile neutropenia	1.5% 8/521 • Number of events 8 • From the start of study drug administration until 12 months after last patient randomized	6.1% 31/508 • Number of events 34 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Haemorrhagic diathesis	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Leukopenia	0.77% 4/521 • Number of events 4 • From the start of study drug administration until 12 months after last patient randomized	0.98% 5/508 • Number of events 5 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Neutropenia	1.5% 8/521 • Number of events 8 • From the start of study drug administration until 12 months after last patient randomized	6.1% 31/508 • Number of events 34 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Pancytopenia	0.38% 2/521 • Number of events 5 • From the start of study drug administration until 12 months after last patient randomized	0.79% 4/508 • Number of events 4 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Thrombocytopenia	2.1% 11/521 • Number of events 11 • From the start of study drug administration until 12 months after last patient randomized	3.3% 17/508 • Number of events 18 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Acute left ventricular failure	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Acute myocardial infarction	0.58% 3/521 • Number of events 3 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Angina pectoris	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.39% 2/508 • Number of events 2 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Atrial fibrillation	0.38% 2/521 • Number of events 2 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Cardiac Arrest	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Cardiac failure	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Cardiopulmonary failure	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.39% 2/508 • Number of events 2 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Myocardial infarction	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Myocardial ischaemia	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Pericardial effusion	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Ventricular fibrillation	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Cardiac disorders Ventricular tachycardia	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Ear and labyrinth disorders Deafness	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Ear and labyrinth disorders Hypoacusis	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Endocrine disorders Adrenal haemorrhage	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Eye disorders Visual acuity reduced	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Eye disorders Vitreious floaters	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Abdominal distension	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Abdominal pain	2.3% 12/521 • Number of events 13 • From the start of study drug administration until 12 months after last patient randomized	1.4% 7/508 • Number of events 7 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Abdominal pain upper	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Ascites	0.77% 4/521 • Number of events 5 • From the start of study drug administration until 12 months after last patient randomized	0.59% 3/508 • Number of events 3 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Constipation	0.58% 3/521 • Number of events 3 • From the start of study drug administration until 12 months after last patient randomized	0.59% 3/508 • Number of events 3 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Diarrhoea	1.7% 9/521 • Number of events 9 • From the start of study drug administration until 12 months after last patient randomized	2.6% 13/508 • Number of events 13 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Dysphagia	0.77% 4/521 • Number of events 4 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Enteritis	0.19% 1/521 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized	0.00% 0/508 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Gastric haemorrhage	0.96% 5/521 • Number of events 5 • From the start of study drug administration until 12 months after last patient randomized	0.79% 4/508 • Number of events 4 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Gastric perforation	0.77% 4/521 • Number of events 4 • From the start of study drug administration until 12 months after last patient randomized	0.79% 4/508 • Number of events 4 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Gastric stenosis	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/521 • From the start of study drug administration until 12 months after last patient randomized	0.20% 1/508 • Number of events 1 • From the start of study drug administration until 12 months after last patient randomized

Other adverse events
Measure	S-1/Cisplatin n=521 participants at risk In the S-1/cisplatin arm, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with a glass of water and prior to cisplatin infusion on Day 1. Cisplatin 75 mg/m2 was administered as a 1- to 3-hour intravenous (IV) infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment.	5-FU/Cisplatin n=508 participants at risk In the 5-FU/cisplatin arm, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles.
Blood and lymphatic system disorders Anaemia	44.0% 229/521 • Number of events 404 • From the start of study drug administration until 12 months after last patient randomized	46.1% 234/508 • Number of events 380 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Neutropenia	28.6% 149/521 • Number of events 383 • From the start of study drug administration until 12 months after last patient randomized	47.2% 240/508 • Number of events 588 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Thrombocytopenia	17.7% 92/521 • Number of events 174 • From the start of study drug administration until 12 months after last patient randomized	22.8% 116/508 • Number of events 190 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Leukopenia	17.5% 91/521 • Number of events 224 • From the start of study drug administration until 12 months after last patient randomized	23.0% 117/508 • Number of events 254 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Lymphopenia	5.0% 26/521 • Number of events 54 • From the start of study drug administration until 12 months after last patient randomized	6.7% 34/508 • Number of events 126 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Granulocytopenia	3.5% 18/521 • Number of events 60 • From the start of study drug administration until 12 months after last patient randomized	2.0% 10/508 • Number of events 19 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Febrile neutropenia	1.9% 10/521 • Number of events 10 • From the start of study drug administration until 12 months after last patient randomized	6.9% 35/508 • Number of events 38 • From the start of study drug administration until 12 months after last patient randomized
Blood and lymphatic system disorders Leukocytosis	1.5% 8/521 • Number of events 13 • From the start of study drug administration until 12 months after last patient randomized	3.0% 15/508 • Number of events 22 • From the start of study drug administration until 12 months after last patient randomized
Ear and labyrinth disorders Tinnitus	5.6% 29/521 • Number of events 76 • From the start of study drug administration until 12 months after last patient randomized	8.7% 44/508 • Number of events 75 • From the start of study drug administration until 12 months after last patient randomized
Ear and labyrinth disorders Deafness	2.1% 11/521 • Number of events 12 • From the start of study drug administration until 12 months after last patient randomized	4.7% 24/508 • Number of events 27 • From the start of study drug administration until 12 months after last patient randomized
Eye disorders Lacrimation increased	6.1% 32/521 • Number of events 62 • From the start of study drug administration until 12 months after last patient randomized	1.2% 6/508 • Number of events 8 • From the start of study drug administration until 12 months after last patient randomized
Eye disorders Vision blurred	3.5% 18/521 • Number of events 81 • From the start of study drug administration until 12 months after last patient randomized	1.8% 9/508 • Number of events 13 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Nausea	61.6% 321/521 • Number of events 778 • From the start of study drug administration until 12 months after last patient randomized	67.3% 342/508 • Number of events 913 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Vomiting	49.9% 260/521 • Number of events 616 • From the start of study drug administration until 12 months after last patient randomized	55.3% 281/508 • Number of events 693 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Diarrhoea	29.2% 152/521 • Number of events 329 • From the start of study drug administration until 12 months after last patient randomized	38.4% 195/508 • Number of events 331 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Abdominal pain	25.1% 131/521 • Number of events 219 • From the start of study drug administration until 12 months after last patient randomized	22.4% 114/508 • Number of events 205 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Constipation	23.0% 120/521 • Number of events 296 • From the start of study drug administration until 12 months after last patient randomized	26.2% 133/508 • Number of events 219 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Abdominal pain upper	12.7% 66/521 • Number of events 125 • From the start of study drug administration until 12 months after last patient randomized	13.2% 67/508 • Number of events 85 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Dyspepsia	8.8% 46/521 • Number of events 86 • From the start of study drug administration until 12 months after last patient randomized	5.9% 30/508 • Number of events 41 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Stomatitis	6.3% 33/521 • Number of events 74 • From the start of study drug administration until 12 months after last patient randomized	30.1% 153/508 • Number of events 321 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Flatulence	6.0% 31/521 • Number of events 49 • From the start of study drug administration until 12 months after last patient randomized	2.0% 10/508 • Number of events 11 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Dysphagia	5.0% 26/521 • Number of events 29 • From the start of study drug administration until 12 months after last patient randomized	8.3% 42/508 • Number of events 54 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Ascites	4.8% 25/521 • Number of events 27 • From the start of study drug administration until 12 months after last patient randomized	2.6% 13/508 • Number of events 15 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Gastrointestinal haemorrhage	3.6% 19/521 • Number of events 19 • From the start of study drug administration until 12 months after last patient randomized	2.8% 14/508 • Number of events 15 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Abdominal distension	3.1% 16/521 • Number of events 23 • From the start of study drug administration until 12 months after last patient randomized	3.5% 18/508 • Number of events 20 • From the start of study drug administration until 12 months after last patient randomized
Gastrointestinal disorders Gastrooesophageal reflux disease	3.1% 16/521 • Number of events 21 • From the start of study drug administration until 12 months after last patient randomized	1.6% 8/508 • Number of events 9 • From the start of study drug administration until 12 months after last patient randomized
General disorders Fatigue	39.3% 205/521 • Number of events 505 • From the start of study drug administration until 12 months after last patient randomized	39.4% 200/508 • Number of events 329 • From the start of study drug administration until 12 months after last patient randomized
General disorders Asthenia	16.9% 88/521 • Number of events 124 • From the start of study drug administration until 12 months after last patient randomized	18.9% 96/508 • Number of events 152 • From the start of study drug administration until 12 months after last patient randomized
General disorders Pyrexia	13.8% 72/521 • Number of events 112 • From the start of study drug administration until 12 months after last patient randomized	12.0% 61/508 • Number of events 80 • From the start of study drug administration until 12 months after last patient randomized
General disorders Disease progression	10.6% 55/521 • Number of events 55 • From the start of study drug administration until 12 months after last patient randomized	6.9% 35/508 • Number of events 35 • From the start of study drug administration until 12 months after last patient randomized
General disorders Oedema peripheral	10.2% 53/521 • Number of events 81 • From the start of study drug administration until 12 months after last patient randomized	9.1% 46/508 • Number of events 56 • From the start of study drug administration until 12 months after last patient randomized
General disorders Performance status decreased	6.7% 35/521 • Number of events 36 • From the start of study drug administration until 12 months after last patient randomized	8.3% 42/508 • Number of events 49 • From the start of study drug administration until 12 months after last patient randomized
General disorders Chest pain	5.2% 27/521 • Number of events 38 • From the start of study drug administration until 12 months after last patient randomized	4.5% 23/508 • Number of events 30 • From the start of study drug administration until 12 months after last patient randomized
General disorders Mucosal inflammation	3.8% 20/521 • Number of events 27 • From the start of study drug administration until 12 months after last patient randomized	29.9% 152/508 • Number of events 330 • From the start of study drug administration until 12 months after last patient randomized
General disorders Chills	3.1% 16/521 • Number of events 20 • From the start of study drug administration until 12 months after last patient randomized	2.0% 10/508 • Number of events 13 • From the start of study drug administration until 12 months after last patient randomized
General disorders Injection site reaction	0.96% 5/521 • Number of events 11 • From the start of study drug administration until 12 months after last patient randomized	3.0% 15/508 • Number of events 21 • From the start of study drug administration until 12 months after last patient randomized
Hepatobiliary disorders Hyperbilirubinaemia	6.1% 32/521 • Number of events 47 • From the start of study drug administration until 12 months after last patient randomized	3.0% 15/508 • Number of events 21 • From the start of study drug administration until 12 months after last patient randomized
Infections and infestations Nasopharyngitis	3.1% 16/521 • Number of events 19 • From the start of study drug administration until 12 months after last patient randomized	1.8% 9/508 • Number of events 9 • From the start of study drug administration until 12 months after last patient randomized
Infections and infestations Oral candidiasis	0.58% 3/521 • Number of events 3 • From the start of study drug administration until 12 months after last patient randomized	4.3% 22/508 • Number of events 31 • From the start of study drug administration until 12 months after last patient randomized
Investigations Weight decreased	28.4% 148/521 • Number of events 157 • From the start of study drug administration until 12 months after last patient randomized	32.3% 164/508 • Number of events 173 • From the start of study drug administration until 12 months after last patient randomized