Phase II study of S-1 monotherapy in paclitaxel- and cisplatin-refractory gastric cancer

S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic the effects achieved with protracted continuous infusion of 5-fluorouracil (5-FU). This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy in patients with paclitaxel- and cisplatin-refractory gastric cancer. The primary end point was progression-free survival; secondary end points were overall survival, safety, and clinical benefit.

Patients were eligible for the study if they had histologically documented gastric adenocarcinoma previously treated with paclitaxel and cisplatin, age > or = 18 years, Eastern Clinical Oncology Group performance status < or =2, adequate organ function, and no evidence of gastrointestinal obstruction or passage disturbance. Patients were treated with a dose of S-1 based on body surface area (BSA) as follows: BSA < 1.25 m(2), 80 mg/day; 1.25 < or = BSA < 1.5 m(2), 100 mg/day; BSA > or= 1.5 m(2), 120 mg/day. The total dose was divided in two and administered twice daily for 4 weeks followed by a 2-week rest period.

Of the 53 patients enrolled in this study, 49 were evaluable. A total of 190 chemotherapy cycles were administered, and the median number of cycles was 2. Five patients (9.4%) had a partial response, and 18 (34%) had stable disease. Median progression-free survival and overall survival were 4.9 and 10.4 months, respectively. Grade 3/4 hematological toxicities included neutropenia in six patients (11%) but no cases of febrile neutropenia were found. Most of the non-hematological toxicities were diarrhea, asthenia, and mucositis, but none reached grade 3 or grade 4 in severity. Improvement of pain was observed in 17 patients (32.1%).

S-1 monotherapy provides active and safe salvage chemotherapy for patients with advanced gastric cancer who have been previously treated with paclitaxel and cisplatin.