Trial of S-1 Plus Cisplatin in Gastric Cancer

The purpose of this study is to evaluate the effectiveness and safety of s-1 plus cisplatin versus 5-FU plus cisplatin as first-line therapy in the treatment of patients with advanced gastric cancer.

This is a randomized, controlled, open-label,multicenter study. Patients are randomized to one of two treatment arms : S-1 plus cisplatin and 5-FU plus cisplatin.

• Drug: s-1 plus cisplatin
  S-1:80 mg/m2/day po twice daily on Day 1-21,cisplatin: 20mg/m2 iv on Day 1-4, repeat every 5 weeks. Number of Cycles: until progression or unacceptable toxicity develops.
  Other Name: Tegafur,Gimeracil and Oteracil Potassium Capsules
• Drug: 5-Fu plus cisplatin

  5-Fu 800 mg/m2/d CI 120h ,Cisplatin 20 mg/m2 as a 2 hour i.v. infusion(on day 1 to day 4 )repeat every 4 weeks.

  Number of Cycles: until progression or unacceptable toxicity develops.

  Other Name: 5-fluoroura

• Experimental: S-1 plus cisplatin
  S-1:80 mg/m2/day po twice daily on Day 1-21,cisplatin: 20mg/m2 iv on Day 1-4, repeat every 5 weeks.Number of Cycles: until progression or unacceptable toxicity develops.
  Intervention: Drug: s-1 plus cisplatin
• Active Comparator: 5-Fu plus cisplatin
  5-Fu 800 mg/m2/d CI 120h ,Cisplatin 20 mg/m2 as a 2 hour i.v. infusion(on day 1 to day 4 )repeat every 4 weeks.Number of Cycles: until progression or unacceptable toxicity develops.
  Intervention: Drug: 5-Fu plus cisplatin

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the stomach with inoperable locally advanced or recurrent and/or metastatic disease.
• Male or female.
• Age 18 -75.
• Previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrolment into the study).
• Measurable disease, according to the Response Evaluation Criteria in Solid Tumours(RECIST)
• ECOG Performance status 0, 1 or 2
• Haematological, Biochemical and Organ Function: Neutrophil count >2.0 × 10 9/L, platelet count > 100 ×10 9/L. Serum bilirubin< 1.5 × upper limit of normal (ULN); or, AST or ALT < 2.5 × ULN (or < 5 × ULN in patients with liver metastases); or, alkaline phosphatase< 2.5 × ULN (or > 5 × ULN in patients with liver metastases,Creatinine clearance > 60 mL/min.
• Signed informed consent.

Exclusion Criteria:

• prior adjuvant/neoadjuvant therapy more than two regiments.
• Received any investigational drug treatment within 30 days of start of study treatment.
• Patients with active gastrointestinal bleeding.
• Neurological toxicity ≥ grade 2 NCI-CTCAE.
• Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
• History or clinical evidence of brain metastases.
• Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes.
• Pregnancy women.
• Subjects with reproductive potential not willing to use an effective method of contraception.
• Patients with known active infection with HIV.
• Known hypersensitivity to any of the study drugs.