SYNOPSIS
Name of Sponsor/Company
Name of Finished ProductName of Active Ingredient
Title of Study

Study centre(s)Publication (reference)
Studied Period
Phase of development
Objectives

Methodology
Number of patients（planned and analyzed）

Diagnosis and main criteria
for inclusion

Test product, dose and modeof administration, batch
numberYakult Honsha Co., Ltd., and Daiichi Sankyo Co., Ltd.
CAMPTO®/Topotecin®
TS-1 capsule®
Irinotecaｎ Hydrochloride Hydrate （CPT-11）
Tegafur/Gimeracil/Oteracil Potassium （S-1）
Randomized phase III study of S-1 plus CPT-11 versus S-1
alone as first line treatment for advanced gastric cancer(GC0301/TOP-002).
54 sites, 56 branches
2008 ASCO Gastrointestinal Cancers Symposium（H.Imamura, et al, Abstract＃5）
From Jun 24, 2004 to May 9, 2007
Phase III
This study was conducted to demonstrate the superiority of
S-1 plus CPT-11 (Arm B) over S-1 alone (Arm A) in terms ofoverall survival, for unresectable or recurrent gastric cancer.
Randomized open-label multi-center phase III clinical study
Planned ： 150 pts per Arm, Total 300 pts.
Analyzed ：Enrolled ： 326 pts （Arm A;162 pts, Arm B;164 pts）
With drug administration ： 319 pts（Arm A;161 pts, Arm B;158 pts）
Full Analysis Set（FAS） ： 315 pts（Arm A;160 pts, Arm B;155 pts）
Safety Analysis Set ： 315 pts（Arm A;160 pts、Arm B;155 pts）
Diagnosis ： Unresectable or recurrent gastric cancer
Inclusion criteria ：① Histologically and/or cytologically confirmed gastriccancer② Ability to take oral medication③ Unresectable or recurrent gastric cancer④ No prior radiotherapy or chemotherapy⑤ Age ranging between 20 and 75 years⑥ An expected survival duration of ≥12 weeks⑦ ECOG performance status 0–2⑧ Adequate organ function⑨ Written informed consent
Arm A ：
S-1 ； Oral S-1 80 mg/m2/day from Day 1 to 28, q6w.
Arm B ：
S-1 ； Oral S-1 80 mg/m2/day from Day 1 to 21.
CPT-11 ； Intravenous irinotecan 80 mg/m2 on Days 1 and15, q5w.
Batch numbers of CPT-11 and S-1 were uncontrolled,because of post-marketing drugs.

Duration of treatment

Criteria for evaluation

Statistical method

Summary - Conclusion

Date of report

Treatment was discontinued in the event of documented
disease progression, unacceptable toxicity, or consent
withdrawal.
Primary endpoint ： Overall survival
Secondary endpoint ：(1) Time to treatment failure（TTF）(2) 1-year survival rate (3) Response rate(RR) (4) Safety
Efficacy ：The difference of overall survival was analyzed using thestratified log-rank test. Probability of survival, median-TTF
and 1-year survival rate was estimated using theKaplan-Meier method. Response rate was evaluated on thebasis of RECIST guidelines, the difference was analyzed
using the chi-square test.
Safety ：In safety analysis set, the incidence of adverse event and side
effect were Estimated, and the frequencies of those werecompiled according to grade.
Efficacy ：Although the median survival time (MST) of Arm A was 318
days and of Arm B was 389 days, Arm B didn’t show
statistically significant superiority to Arm A (log-rank testp=0.234). The median-TTF were 111 days in Arm A and 138
days, Arm B didn’t show statistically significant superiority
to Arm A (log-rank test p=0.157). The 1-year survival rates
were 44.9% in Arm A and 52.0% in Arm B. RR was
statistically significant different (Arm A/B, 26.9%/41.5%;
chi-square test p=0.035) in 187 RECIST evaluable pts.
Safety ：Grade 3/4 adverse events over 3 percent in Arm A wereanorexia 18.8%, hemoglobin 11.9%, neutrophils 10.6%,
fatigue 7.5%, hyponatremia 6.9%, diarrhea 5.6%, nausea
5.6%, bilirubin 5.6%, AST (SGOT) 5.0%, hypocalcemia 5.0%,
platelets 3.8%, hypoalbuminemia 3.8%, infection/febrileneutropenia 3.8%, pain 3.8%, leukocytes 3.1%, ileus 3.1%,
those of in Arm B were neutrophils 27.1%, anorexia 17.4%,
diarrhea 16.1%, hemoglobin 15.5%, leukocytes 11.6%,
hyponatremia 7.7%, nausea 7.1%, fatigue 6.5%, hypokalemia
4.5%, dehydration 3.2%, vomiting 3.2%, bilirubin 3.2%, AST(SGOT) 3.2%, febrile neutropenia 3.2%. Treatment-related
death was documented 2 patients in Arm B.
Conclusion ：Although S-1 plus CPT-11 didn’t show statisticallysignificant superiority to S-1 alone in overall survival ofprimary endpoint, RR and MST were not inferior to those ofphase III clinical study reported recently both domesticallyand internationally. In safety, S-1 alone and S-1 plus CPT-11
were well tolerable.
Sept 30, 2009
（Sept 30, 2009）