Eligibility

Patients with histologically documented, inoperable, locally advanced or metastatic adenocarcinoma of the stomach and the GEJ, aged >18 years old, were eligible for the study. No prior chemotherapy for metastatic disease was allowed; adjuvant chemotherapy or chemo-radiotherapy was allowed provided that at least 6 months had elapsed since the completion of the treatment. Other key eligibility criteria were: absence of HER2 expression (score 1 by immunocytochemistry [ICH] or fluorescence in situ hybridization-negative for those with score 2 by ICH); measurable target lesions as defined according to the RECIST criteria (RECIST v.1.1) (patients with non-measurable disease could be enrolled only in the phase I part of the study); ECOG performance status 0-2, adequate bone marrow (defined by hemoglobin ≥8 g/dL, white blood cells ≥3×10⁹/L, neutrophil count ≥1.5×10⁹/L, platelets ≥100×10⁹/L), renal (creatinine clearance ≥50 mL/min) and liver function tests (total bilirubin ≤1.5 times the institutional upper limit of normal, and aspartate/alanine transaminases and alkaline phosphatase ≤2.5 time the upper limit of normal); and estimated life expectancy >3 months. All patients gave written informed consent before their enrollment in the study. The protocol was approved by the Ethics and Scientific Committees of the participating institutions, as well as by the Greek National Organization for Medicines (EOF) and the National Ethics Committee (EED).