Docetaxel: a taxoid for the treatment of metastatic breast cancer.

Abstract

The pharmacology, pharmacokinetics, clinical trials, adverse effects, and dosage and administration of docetaxel are reviewed. Docetaxel, a taxoid for the treatment of metastatic breast cancer, blocks the ability of tumor cells to divide in the M phase of the cell cycle. The drug has demonstrated superior cytotoxic activity in the treatment of a variety of cancers and enhanced activity in combination with other drugs. The pharmacokinetics of docetaxel appear to be linear. There seems to be a large interpatient variation in docetaxel biotransformation rates. Docetaxel has FDA-approved labeling for use in the treatment of patients with locally advanced or metastatic breast cancer whose disease has progressed during anthracycline-based therapy or who have relapsed during anthracycline-based adjuvant therapy. Phase II trials established the drug's role in first-line and second-line treatment of advanced breast cancer and as therapy for anthracycline-resistant advanced breast cancer, and they suggested a role for the agent in combination chemotherapy. The dose-limiting toxicity in all studies has been neutropenia. Other commonly noted adverse effects include mucositis, hypersensitivity reactions, and neuropathy. The recommended dosage for patients with metastatic or locally advanced breast cancer and normal hepatic function is 60-100 mg/m2 i.v. infused over one hour every three weeks. Docetaxel is not recommended for patients with liver metastases or impaired liver function because clearance of the drug is impaired. Docetaxel is effective in the treatment of metastatic and anthracycline-resistant breast cancer and may have a role in combination with other agents and in neoadjuvant and adjuvant therapy.