Capecitabine/vinorelbine:: An effective and well-tolerated regimen for women with pretreated advanced-stage breast cancer

Background: The combination of capecitabine and vinorelbine is a potentially valuable treatment regimen for patients with advanced-stage breast cancer. The drugs are easy to administer and do not cause significant alopecia. In order to identify the spectrum of toxicity of a regimen containing 2 drugs, we conducted an extended phase I study aimed at defining maximum tolerated doses, recommended doses, safety; and efficacy in patients with pre-treated advanced-stage breast cancer. Patients and Methods: Forty-nine patients with advanced-stage breast cancer were treated with escalating doses of oral capecitabine from 500 mg/m(2) to 1375 mg/m(2) twice daily on days 1-14 and escalating doses of vinorelbine from 12.5 mg/m(2) to 25 mg/m(2) intravenously (I.V) on days 1 and 3 every 3 weeks. Almost all patients (90%) had received >= 3 previous treatments for metastatic disease (anthracyclines, 76%; 5-flourouracil, 76%; taxones, 29%). Results: Dose level 9 (capecitabine 1250 mg/m(2) twice daily on days 1-14 and vinorelbine 22.5 mg/m(2) I.V on days 1 and 3) was identified as the maximum tolerated dose. The most frequent clinical adverse events were nausea (78%), asthenia (59%), constipation (51%), mucositis (47%), and hand-foot syndrome (41%). The majority of events were mild to moderate; the only grade 4 clinical adverse events were diarrhea, fever, and thromboembolism, each of which occurred in I patient (2%) at dose level 8. Objective confirmed responses were observed in 18 patients (37%), including I complete response (2%) and 17 partial responses (35%). Disease was stable in an additional 10 patients (20%), with a median duration of 6.3 months (range, 4-24 months). Conclusion: The combination of the 2 drugs is very well tolerated and effective, especially considering the previous exposure to chemotherapy. The recommended dose for further phase 11 studies should be capecitabine 1250 mg/m(2) twice daily on days 1-14 and vinorelbine 22.5 mg/m(2) I.V. on days 1 and 3.