Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer

Purpose: A dose-escalation study of irinotecan hydrochloride (CPT-II) combined with fixed-dose cisplatin wets conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. Patients and Methods: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 wets administered as a 90-minute intravenous (IV) infusion, which was followed 2 hours later by a 120-minute IV infusion of cisplatin 80 mg/m(2). CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m(2), and was escalated in increments of 10 mg/m(2) until severe or life-threatening toxicity wets observed. Results: The MTD of this combination was CPT-11 80 mg/m(2). At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/mu L, 66.7% (eight of 12) had neutropenia of less than 500/mu L, and 16.7% (two of 12) herd severe diarrhea of grade 4 during the first course. The dose-limiting toxicity wets neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). Conclusion: The recommended dose and schedule is CPT-11 70 mg/m(2) on days 1 and 15 and cisplatin 80 mg/m(2) on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study. (C) 1997 by American Society of Clinical Oncology.