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Annals of Oncology 14:1442-1448, 2003
© 2003 European Society for Medical Oncology

Original Paper

Capecitabine and irinotecan as first-line chemotherapy in patients with metastatic colorectal cancer: results of an extended phase I study{dagger}

M. Tewes1, N. Schleucher1, W. Achterrath2, H. J. Wilke1, S. Frings3, S. Seeber1, A. Harstrick1, Y. M. Rustum4 and U. Vanhoefer1,+,§

1 Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School, Essen; 2 Aventis, Department of Clinical Research, Oncology, Bad Soden, Germany; 3 Hoffmann-La Roche, Nutely, NJ; 4 Department of Molecular Pharmacology and Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY, USA

Received 11 March 2003; revised 3 May 2003; accepted 3 June 2003

Background:

To define the maximum-tolerated dose (MTD) and to evaluate the dose-limiting toxicities (DLTs) of the combination of capecitabine and irinotecan in patients with metastatic colorectal cancer.

Patients and methods:

Thirty-seven patients with measurable metastatic colorectal cancer with no prior chemotherapy for metastatic disease were treated at three dose levels (DLs). For the first two dose levels, irinotecan (70 mg/m2) was administered once a week for 6 weeks in combination with 2 weeks of capecitabine at 1000 mg/m2 (DL1) or 1250 mg/m2 (DL2) twice daily, starting on days 1 and 22. In the last dose escalation step, the dose of irinotecan was increased to 80 mg/m2 (DL3). One cycle lasted 7 weeks.

Results:

In the subsequent phase I trial, 96 cycles of capecitabine and irinotecan were administered. At DL3, three out of six patients experienced DLTs (diarrhea, neutropenia, asthenia). In order to confirm the safety of the recommended dose, DL2 was extended to 15 patients. Five patients (33%) showed DLTs at this dose level, which was considered too high to embark on further clinical studies. Subsequently, the starting dose (DL1) was extended to a total of 16 patients, with diarrhea being the main toxicity. The overall response rate was 38% [95% confidence interval (CI) 21% to 58%], with a median response duration of 8.7 months (95% CI 6.4–11.5 months).

Conclusions:

The recommended doses for further studies are irinotecan 70 mg/m2 and capecitabine 1000 mg/m2. The combination of capecitabine and irinotecan appears to have significant therapeutic efficacy with manageable toxicity.

Key words: capecitabine, colorectal cancer, irinotecan, phase I study


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