Tankanow R M
College of Pharmacy, University of Michigan Hospital Pharmacy, Ann Arbor 48109, USA.
Am J Health Syst Pharm. 1998 Sep 1;55(17):1777-91. doi: 10.1093/ajhp/55.17.1777.
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.
本文综述了多西他赛的药理学、药代动力学、临床试验、不良反应以及剂量与用法。多西他赛是一种用于治疗转移性乳腺癌的紫杉烷类药物，可阻断肿瘤细胞在细胞周期M期的分裂能力。该药物在治疗多种癌症方面已显示出卓越的细胞毒性活性，并且与其他药物联合使用时活性增强。多西他赛的药代动力学似乎呈线性。多西他赛的生物转化速率在患者之间似乎存在很大差异。多西他赛已获得美国食品药品监督管理局（FDA）批准的标签，用于治疗局部晚期或转移性乳腺癌患者，这些患者的疾病在基于蒽环类药物的治疗期间进展，或在基于蒽环类药物的辅助治疗期间复发。II期试验确定了该药物在晚期乳腺癌一线和二线治疗以及蒽环类耐药晚期乳腺癌治疗中的作用，并提示该药物在联合化疗中的作用。所有研究中的剂量限制性毒性均为中性粒细胞减少。其他常见的不良反应包括粘膜炎、过敏反应和神经病变。转移性或局部晚期乳腺癌且肝功能正常的患者推荐剂量为60 - 100mg/m²，静脉滴注1小时，每三周一次。不推荐肝转移或肝功能受损的患者使用多西他赛，因为该药物的清除会受到损害。多西他赛在治疗转移性和蒽环类耐药乳腺癌方面有效，并且可能在与其他药物联合以及新辅助和辅助治疗中发挥作用。
