Phase I study of docetaxel, cisplatin and S-1 in patients with advanced gastric cancer.

Objective: S-1 plus cisplatin is standard treatment for advanced gastric cancer in Japan. Triplet therapy with docetaxel, cisplatin and fluoropyrimidine showed a survival benefit over doublet therapy, but was associated with substantial toxicities. We investigated the maximum tolerated dose of combination chemotherapy with divided-dose docetaxel added to standard-dose S-1 plus cisplatin in advanced gastric cancer patients.

Methods: Patients with advanced gastric cancer, naive to chemotherapy or not refractory to fluoropyrimidine, were enrolled. Fixed doses of S-1 (40 mg/m(2) twice daily for 3 weeks) and cisplatin (60 mg/m(2) on day 1) were administered with increasing docetaxel dose levels of 20 mg/m(2) (dose level 1), 25 mg/m(2) (dose level 2) and 30 mg/m(2) (dose level 3) on days 1, 8 and 15, or 40 mg/m(2) (dose level 4) on days 1 and 15 of a 5-week cycle. Treatment cycles were repeated until disease progression, patient's refusal or unacceptable toxicity occurred.

Results: Fifteen patients were enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, grade 3 febrile neutropenia was seen in one patient. At dose level 4, grade 3 infection and grade 3 abdominal pain were observed. Thus, dose level 4 was determined to be the maximum tolerated dose. The response rate was 54% (7/13), and median progression-free survival and overall survival were 243 and 383 days, respectively.

Conclusions: The recommended dose of docetaxel added to standard-dose S-1 (80 mg/m(2) days 1-21) plus cisplatin (60 mg/m(2) day 1) was 40 mg/m(2) on days 1 and 15 of a 5-week cycle.