A phase I dose-escalating and pharmacokinetic study of docetaxel and vinorelbine as first-line chemotherapy for metastatic breast cancer.

Docetaxel and vinorelbine are both active drugs as single agents in the treatment of metastatic breast cancer. We performed a phase I dose-escalating and pharmacokinetic study to assess the safety profile of a new combination regimen and the pharmacokinetic interaction of vinorelbine and docetaxel. Patients with metastatic breast cancer received first-line treatment with both drugs on days 1-5. Treatment was restarted on day 21 of each cycle. We had to stop the escalation at the first step of the study (vinorelbine 20 mg/m(2) followed by docetaxel 30 mg/m(2) on days 1 and 5) because of hematological toxicity. In 4 additional patients who received G-CSF supplementation, no major leukopenia occurred, suggesting that the toxicity profile of this combination is very homogenous and focused on neutrophils. We found no pharmacokinetic interaction between the two drugs. These results suggest that a pharmacodynamic interaction was the cause of the hematological toxicity and that sequential regimens should be preferably further explored.