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 max imum-tolerated dose (MTD), dose-limiting toxicities, and objective res ponse rate in patients with advanced gastric cancer. Patients and Meth ods: Twenty-four patients with or without prior chemotherapy were enro lled. 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 cispl atin 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 prog ression was observed. The initial dose of CPT-11 was 60 mg/m(2), and w as escalated in increments of 10 mg/m(2) until severe or life-threaten ing toxicity wets observed. Results: The MTD of this combination was C PT-11 80 mg/m(2). At this dose level, 16.7% of patients (two of 12) ha d leukopenia of less than 1,000/mu L, 66.7% (eight of 12) had neutrope nia 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 ne utropenia. Ten patients achieved a partial response (PR), and the over all response rate was 41.7% among 24 patients (95% confidence interval , 21.9% to 61.4%). Conclusion: The recommended dose and schedule is CP T-11 70 mg/m(2) on days 1 and 15 and cisplatin 80 mg/m(2) on day 1 eve ry 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, shou ld be further assessed in a phase II study. (C) 1997 by American Socie ty of Clinical Oncology.