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/m(2) 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/m(2) (dose level 1) and 30 mg/m(2) (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.
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/m(2) 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/m(2) (dose level 1) and 30 mg/m(2) (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.
Authors: Simon P Gampenrieder; Rupert Bartsch; Peter Matzneller; Ursula Pluschnig; Peter Dubsky; Michael X Gnant; Christoph C Zielinski; Guenther G Steger Journal: Breast Care (Basel) Date: 2010-05-27 Impact factor: 2.860
Authors: Volkmar Müller; Christoph Thomssen; Marcus Schmidt; Manfred Glados; Christian Jackisch; Volker Heilmann; Axel Hinke; Antje Lehnert; Henryk Borowicz; Volker Möbus Journal: BMC Cancer Date: 2010-08-16 Impact factor: 4.430
Authors: N Tubiana-Mathieu; P Bougnoux; D Becquart; A Chan; P-F Conte; F Majois; M Espie; M Morand; N Vaissiere; G Villanova Journal: Br J Cancer Date: 2009-07-07 Impact factor: 7.640