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.