Summary Treatment of patients affected by metastatic gastric cancer with low performance status (PS) is a very hard choice. It is mandatory to define a very well-tolerated schedule to be employed in these subgroup of patients. Patients and Methods From June 1999 to December 2001, 21 patients (pts) affected by metastatic gastric cancer with low performance status (≥2 ECOG) were treated with bimonthly “de Gramont” schedule. Treatment was planned to perform 6 courses of chemotherapy for each patient plus other 2-4 if a response had been documented. Results A total of 161 courses of de Gramont schedule was administered to the 21 pts enrolled. We observed 8 PD (38%), 8 SD (38%), 5 objective responses (24% – 2 MR, 3 PR). Duration of objective responses (OR) was 5 months, 3 months for 3 PRs and 2 and 1 months for two MRs respectively. At time of observation (June 2002) median overall survival (OS) was 14 months, median survival from the starting de Gramont schedule was 8 months. Toxicity was very mild: grade 3 leukopenia in 1 pt, grade 1-2 anemia and piastrinopenia in 3 pts, grade 1-2 nausea vomiting in 5 pts, grade 1 diarrhea in 4 pts, grade 3 mucositis in 2 pts. No other side effect was renowned. PS ameliorated in 12 (57%) pts, even if a major response was not noted. Conclusions de Gramont schedule can be safely and effectively employed in metastatic gastric cancer pts with very low performance status.