© 2005 European Society for Medical Oncology
Original article |
Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer
1 Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Duisburg-Essen Medical School, Essen; 2 Department of Gynecology and Obstetrics, University of Frankfurt, Frankfurt; 3 Department of Gynecology and Obstetrics, University of Duisburg-Essen Medical School, Essen, Germany
* Correspondence to: Dr U. Vanhoefer, Department of Internal Medicine (Medical Oncology), Marienkrankenhaus, Alfredstrasse 9, 22087 Hamburg, Germany. Tel: +49-40-2546-2501; Fax: +49-40-2546-2500; Email: vanhoefer.innere{at}marienkrankenhaus.org
Purpose: To define the maximum-tolerated dose (MTD) and to evaluate the dose-limiting toxicities (DLT) of the combination of capecitabine and vinorelbine in patients with metastatic breast cancer who relapse after adjuvant and/or first-line treatment. In addition, we aimed to obtain data on efficacy and safety at the recommended dose.
Patients and methods: Patients with measurable metastatic breast cancer after failure of prior chemotherapy (including anthracyclines and/or taxanes) were eligible. Capecitabine was administered with a fixed dose of 1000 mg/m2 orally twice daily for 2 weeks followed by 1 week rest. One treatment cycle consisted of 6 weeks of treatment containing two treatment periods of capecitabine. Vinorelbine was given intravenously at escalated doses of 25 mg/m2 (dose level 1) and 30 mg/m2 (dose level 2) on days 1 and 8, and 22 and 29.
Results: Thirty-three patients received a total of 91 cycles of capecitabine and vinorelbine. The median number of administered cycles per patient was three (range one to six). Thirty-one patients were evaluable for toxicity. At dose level 2 four out of seven patients experienced DLTs (nausea/vomiting, febrile neutropenia, grade 4 neutropenia, infection and diarrhea); thus, the MTD was defined. In order to confirm the safety and efficacy, dose level 1 was extended to 24 patients. Two patients [8.3%; 95% confidence interval (CI) 1% to 27%] showed DLTs (hospitalization due to febrile neutropenia and prolonged neutropenia). The main toxicity was neutropenia, which was observed at National Cancer Institute Common Toxicity Criteria grade 3 and 4 in 39% of patients. The overall response rate for capecitabine and vinorelbine was 55% (95% CI 36% to 72.7%), including three patients with a complete remission. The median time to disease progression was 8 months (95% CI 4.3–11.7) with an overall survival of 19.2 months (95% CI 11.3–27.1) based on intention-to-treat analysis.
Conclusions: The combination of capecitabine and vinorelbine can be administered with manageable toxicity and showed significant efficacy for patients with metastatic breast cancer even after failure of a anthracycline- and/or taxane-based therapy.
Key words: breast cancer, capecitabine, phase I/II study, vinorelbine
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