A Novel Combination of Cisplatin, Irinotecan, and Capecitabine in Patients with Advanced Cancer

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• 作者：Michael Jefford ; Michael Michael ; Mark A. Rosenthal ; Ian D. Davis ; Michael Green ; Bev McClure ; Jennifer Smith ; Brigid Waite and John Zalcberg
• 关键词：clinical trials ; phase I ; cisplatin ; irinotecan ; capecitabine
• 刊名：Investigational New Drugs
• 出版年：2004
• 出版时间：2004
• 年：2004
• 卷：22
• 期：2
• 页码：185-192
• 全文大小：71 KB

文摘

Background: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. Patients and methods: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1–14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (4080mg/m2) and capecitabine (10003300mg/d) combined with a fixed dose of cisplatin (30mg/m2). Part B: escalating doses of irinotecan (MTD-AMTD-A+40mg/m2) with fixed doses of cisplatin (20mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300mg/d2600mg/d) with fixed doses of cisplatin (20mg/m2) and irinotecan (60mg/m2). Results: Of 51 eligible patients 27 (53 % ) were male, median age was 58 years and 88 % had PS 0–1. Major primary disease sites were colorectal (24 % ), unknown (14 % ), stomach (14 % ), and pancreas (12 % ). MTD-A was cisplatin 30mg/m2, irinotecan 60mg/m2, capecitabine 1000mg/d and MTD-B was cisplatin 20mg/m2, irinotecan 90mg/m2, capecitabine 1000mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of 2 weeks or 25 % dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53 % ), twelve PD (24 % ) and five NE (10 % ). Conclusion: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.