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 (40 --> 80 mg/m2) and capecitabine (1000 --> 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A --> MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d-->2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/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 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/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 > or = 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.