Pilot study of vinorelbine (Navelbine) and paclitaxel (Taxol) in patients with refractory breast cancer and lung cancer.

Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) and paclitaxel (Taxol; Bristol-Myers Oncology, Princeton, NJ) as single-agent therapy exhibit good activity in breast and lung cancers. Concurrent administration of vinorelbine and paclitaxel achieves synergistic cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells in vitro. Because these agents bind to distinct sites on tubulin and affect microtubules in opposite ways, a pilot study was conducted of the combination of vinorelbine and paclitaxel in patients with metastatic breast cancer or lung cancer who were refractory to first-line chemotherapy. Entry criteria included measurable disease, a Karnofsky performance status of > or = 70, adequate bone marrow reserve, adequate hepatic and renal functions, and no central nervous system metastasis. Seven patients entered the study (one with breast cancer and six with lung cancer; three men and four women, with an age range of 39 to 79 years). The first three patients received vinorelbine 25 mg/m2 intravenously for 5 to 10 minutes on days 1 and 8, and paclitaxel 90 mg/m2 intravenously over 3 hours on day 1 after the administration of vinorelbine. Premedication prior to paclitaxel consisted of dexamethasone, cimetidine, and diphenhydramine. The subsequent four patients enrolled in the study received the identical dose of vinorelbine, but the paclitaxel dose was increased to 175 mg/m2 in the same sequence. Patients received granulocyte colony-stimulating factor 5 micrograms/kg subcutaneously from days 3 to 17 (except day 8) or until the absolute granulocyte count was 10,000/microL or higher. Preliminary results showed that one of the first three patients developed grade 4 neutropenia and grade 5 infection. In the subsequent four patients, there were two grade 3 and two grade 4 cases of neutropenia; leukopenic fever or infection did not occur. Two patients required red blood cell transfusions. Two patients developed grade 1 and one patient developed grade 2 peripheral neuropathy. Myalgia and fatigue were common but self-limited. The one patient with breast cancer had a partial response; no response was noted in the lung cancer patients.