Phase I study of Doxil and vinorelbine in metastatic breast cancer

Vinorelbine and Doxil (liposomal doxorubicin) are active chemotherapeutic agents in metastatic breast cancer. A phase I study was designed to evaluate combination therapy.

Thirty women with metastatic breast cancer were enrolled. Dose-limiting toxicity was determined through a dose escalation scheme, and defined for the first treatment cycle, only. Pharmacokinetic studies were performed during the first cycle of treatment.

In the first cohort of Doxil 30 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8, patients experienced severe neutropenia. Vinorelbine administration was changed thereafter to days 1 and 15 of each cycle. Dose limiting toxicity was observed at Doxil 50 mg/m2 and vinorelbine 25 mg/m2. Doxil 40 mg/m2 and vinorelbine 30 mg/m2 was defined as the maximally tolerated dose. Few toxicities (principally neutro penia) were seen at this dose level, with the notable absence of significant nausea, vomiting, or alopecia. Though 63% of patients had received prior anthracycline-based chemotherapy, only one patient developed grade 2 cardiac toxicity. Pharmacokinetic studies revealed prolonged exposure to high doxorubicin concentrations for several days following Doxil administration.

Combination chemotherapy with Doxil and vinorelbine affords treatment with two active drugs in women with metastatic breast cancer, and appears to have a favorable toxicity profile. A schedule of Doxil 40 mg/m2 day 1 and vinorelbine 30 mg/m2 days 1 and 15 given every 28 days is recommended for phase II studies.