Trial of 3-weekly Versus 5-weekly Schedule of S-1 Plus Cisplatin in Gastric Cancer: SOS

• Histologically documented metastatic or recurrent gastric adenocarcinoma including adenocarcinoma of the gastro-esophageal junction
• Age 18 to 74 years old
• Performance status (ECOG scale) 0-2
• No significant problems for oral intake and drug administration
• At least one measurable or evaluable disease defined by RECIST
• Adequate bone marrow function (ANC ≥ 1,500/uL, Platelet ≥ 100,000/ uL, Hb ≥ 9.0 g/dl)
• Adequate renal function: serum creatinine ≤ UNL (if serum creatinine > UNL, creatinine clearance should be ≥ 60 mL/min)
• Adequate hepatic function (Total bilirubin \< 2 x UNL and AST/ALT levels \< 3 x UNL without liver metastasis,total bilirubin \< 3x ULN and AST/ALT levels \< 5 x UNL with liver metastasis)
• Prior systemic therapy (for instance, cytotoxic chemotherapy or active/passive immunotherapy) is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrolment into the study) and cisplatin was not used before
• Patients should sign a written informed consent before study entry

Exclusion Criteria:

• Tumor type other than adenocarcinoma
• Previously exposed to any fluropymidine within 6 months before the study
• Previously exposed to Platinum therapy regardless of its period and/or duration
• Microscopic residual disease only after noncurative gastrectomy with R1 resection (resection margin positive)
• Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence)
• Prior radiotherapy was administered to target lesions selected for this study, or radiotherapy to the non-target lesions has been completed within 4 weeks before randomization
• Presence of CNS metastasis
• Major surgery within 4 weeks before initiation of study treatment or lack of complete recovery from the effects of major surgery (patient received curative operation or RFA for metastatic disease)

• Serious illness or medical conditions:

  • Congestive heart failure (NYHA class III or IV)
  • Unstable angina or myocardial infarction within the past 12 months
  • Significant arrhythmias requiring medication and conduction abnormality such as over 2nd degree AV block
  • Uncontrolled hypertension
  • Hepatic cirrhosis (≥ Child class B)
  • Interstitial pneumonia
  • Pulmonary adenomatosis
  • Psychiatric disorder that may interfere with protocol compliance
  • Unstable diabetes mellitus
  • Uncontrolled ascites or pleural effusion
  • Active infection

• Receiving a concomitant treatment interacting with S-1 or cisplatin:

  • Flucytosine (a fluorinated pyrimidine antifungal agent)
  • Antivirals such as sorivudine, ramivudine, brivudine or other chemically related agents, warfarin, phenprocoumon, phenytoin, allopurinol
• Pregnant or lactating woman
• Women of child bearing potential not using a contraceptive method
• Sexually active fertile men not using effective birth control during medication of study drug and up to 6 months after completion of study drug if their partners are women of child-bearing potential
• Any patients judged by the investigator to be unfit to participate in the study