Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer.

Abstract

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: A Welt, G von Minckwitz, C Oberhoff, D Borquez, R Schleucher, S Loibl, A Harstrick, M Kaufmann, S Seeber, U Vanhoefer
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 16 Issue 1 Pg. 64-9 (Jan 2005) ISSN: 0923-7534 [Print] England
• PMID: 15598940 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxycytidine
• Vinblastine
• Capecitabine
• Vinorelbine
• Fluorouracil

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Capecitabine
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Fluorouracil (analogs & derivatives)
• Humans
• Infusions, Intravenous
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis
• Neutropenia (chemically induced)
• Treatment Outcome
• Vinblastine (administration & dosage, analogs & derivatives)
• Vinorelbine