Table 1 Inclusion and exclusion criteria

 1. Signed written informed consent incl. participation in translational research

 2. Male or female patient 18 years or older

 3. Histologically confirmed metastatic or locally advanced unresectable gastric adenocarcinoma or adenocarcinoma of the esophagus or the esophagogastric junction (Her-2/neu negative or with unknown Her-2/neu status)

 4. Adjuvant/neoadjuvant or perioperative chemotherapy or (chemo-)radiotherapy must have been finished at least 6 months before start of the induction therapy

 5. For patients enrolled before induction therapy: No previous systemic treatment (i.e. chemotherapy) for metastatic disease

 6. For patients enrolled after induction therapy: Having finished a three-months induction therapy (6 cycles of a bi-weekly regimen, 4 cycles of a three-weekly regimen or 3 cycles of a four-weekly regimen) without tumour progression or limiting toxicity

 7. ECOG Performance Score 0–1 (Karnofsky Performance status > = 80%)

 8. Ability for oral intake of the study drug, patients with tumour-related problems with oral intake might be registered if the symptom is expected to be improved during induction therapy (e.g. due to a tumour stenosis)

 9. Female patient of childbearing potential (i.e. did not undergo surgical sterilization – hysterectomy, bilateral tubal ligation, or bilateral oophorectomy - and is not post-menopausal for at least 24 consecutive months) with a negative pregnancy test

 10. Hematology and biochemistry laboratory results within the limits normally expected for the patient population, defined by the following:

• Absolute neutrophil count ≥1500/μl

• Platelet count ≥100,000/μl

• Leukocyte count >3000/μl

• Hemoglobin ≥9 g/dL or 5.59 mmol/l, previous transfusions (>3 days) of erythrocytes are allowed

• Total bilirubin ≤1.5 times the upper limit of normal (ULN), in patients with known Meulengracht syndrom ≤3 x ULN

• AST ≤ 3xULN in absence of liver metastases, or ≤5xULN in presence of liver metastases

• ALT ≤3xULN in absence of liver metastases, or ≤5xULN in presence of liver metastases

• Creatinine clearance ≥30 mL/min according to Cockcroft-Gault formula

1. Previous major sugery within the last 28 days before the start of the induction treatment. The implantation of a central venous access (e.g. porth-a cath system) or a diagnostic laparoscopy are allowed.

2. History of other malignant tumours within the last 5 years before start of induction treatment, except basal cell carcinoma or curatively excised cervical carcinoma in situ

3. Known brain metastases

4. Concurrent radiotherapy involving target lesions used for this study. Concurrent palliative radiation for non-target lesions is allowed if other target lesions are available outside the involved field; previous radiotherapy including target lesions must have been finished at least 28 days before start of induction treatment.

5. For patients enrolled before the induction therapy: Previous systemic treatment (i.e. chemotherapy) for metastatic disease

6. Known active HBV, HCV infection or documented HIV infection

7. Serious concomitant disease or medical condition that by judgment of the Investigator renders the patient at high risk of treatment complications

8. Clinically relevant coronary artery disease (NYHA functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the last 3 months or high risk of uncontrolled arrhythmia

9. Female patient pregnant or breast feeding

10. Female patient of childbearing potential (i.e. did not undergo surgical sterilization – hysterectomy, bilateral tubal ligation, or bilateral oophorectomy - and is not post-menopausal for at least 24 consecutive months) not willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the end of treatment. Male patient not willing to use an adequate method of contraception to avoid conception throughout the study and for up to 26 weeks after the end of treatment in such a manner that the risk of pregnancy is minimized.

11. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 60 days prior to start of induction (e.g. one of the allowed standard chemotherapies (see above) with or without additional placebo within a clinical trial is allowed)

12. Chronic diarrhea or short bowel syndrome

13. Known hypersensitivity to S-1, other fluoropyrimidines or platinum compounds. Contraindication to receive S-1 or the polychemotherapy (induction & arm B) chosen for this patient as per current Summary of Product Characteristics. Known DPD deficiency

14. For patients enrolled before the induction therapy: Grade ≥ 2 peripheral neuropathy

15. Known drug abuse/alcohol abuse