A phase II trial of fractionated vinorelbine/doxorubicin as first-line therapy for advanced breast cancer

In western countries breast cancer is still the leading cause of death of w omen. Very promising results have been obtained by combining vinorelbine an d doxorubicin, two of the most active drugs in metastatic breast cancer How ever, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity mainly due to the total cumulative doses of a nthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut do wn its toxicity while maintaining the same activity. Fifty-two chemotherapy naive patients with metastatic breast cancer. entered into the study and w ere treated with vinorelbine 25 mg/m(2) plus doxorubicin 25 mg/m(2) both on days I and 8 every three weeks. Fifty-one patients were eligible and evalu able for toxicity while 47 of them were evaluable for activity. Haematologi cal toxicity was predominantly related to neutropenia, with grade 3/4 in 16 % of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65 % of the patients), local phlebitis and severe constip ation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity 38 out of 47 patients (80 %) responded to therapy, Mine of them achieving complete responses (19 %). Median respon se duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorub icin is associated with excellent haematological and non-haematological tol erability (especially as regards cardiac toxicity), coupled with high level s of activity comparable to those observed using regimens based on unfracti onated administration of treatment.