Phase I trial of weekly docetaxel with a 4-weekly cisplatin administration in patients with advanced gastric carcinoma

The docetaxel-cisplatin combination is active against several tumors including gastric cancer but it is followed by severe myelosuppression. Recent experience with weekly taxanes has demonstrated a mild myelotoxicity with high dose intensity. We investigated in a phase I study a weekly schedule of docetaxel on days 1, 8 and 15 and cisplatin on day 1 every 4 weeks in 19 patients with advanced gastric cancer with no prior chemotherapy. Cohorts of patients were treated with escalating doses of docetaxel (starting dose 30 mg/m² per week and increments of 10 mg/m² per week) and cisplatin (starting dose 70 mg/m² and increments of 5 mg/m²). Febrile neutropenia was the only dose-limiting event occurring in four (20%) patients; the dose-limiting toxicity was reached at dose level three (docetaxel 40 mg/m² per week and cisplatin 75 mg/m²). The maximum-tolerated dose was 40 mg/m² per week for docetaxel and 70 mg/m² every 4 weeks for cisplatin. Grade 3/4 neutropenia occurred in six patients (30%); early death occurred in one patient with septic shock because of neutropenia and another with acute coronary ischemia. Two (11%) complete and two (11%) partial responses were documented (ORR 22%; 95% CI 3–39%), with a median response duration of 5 months and median time to progression of 7 months. In conclusion, the combination of weekly docetaxel plus cisplatin is feasible with moderate toxicity and merits further investigation in phase II studies in advanced gastric cancer.Presented as an abstract at the 15th International Congress on Anti-Cancer Treatment, Paris, 9–12 February 2004.