Hainsworth J D, Burris H A, Greco F A
Sarah Cannon-Minnie Pearl Cancer Center, Nashville, TN 37203, USA.
Semin Oncol. 1999 Jun;26(3 Suppl 10):19-24.
Docetaxel (Taxotere; Rhône-Poulence Rorer, Antony, France) is a highly efficacious antineoplastic agent; however, its administration every 3 weeks produces substantial myelosuppression. Based on recent observations that the administration of paclitaxel on a weekly schedule minimizes myelosuppression, investigation of weekly docetaxel has been initiated. A recently completed phase I study of weekly docetaxel demonstrates markedly decreased myelosuppression with this schedule. The maximum tolerated dose was 43 mg/m2/wk; with this dose, myelosuppression was mild and the dose-limiting toxicity was fatigue/asthenia. Other nonhematologic toxicities were uncommon when doses of less than 40 mg/m2/wk were administered. Edema was not observed, in spite of an abbreviated dexamethasone schedule (8 mg every 12 hours for three doses, beginning 12 hours before docetaxel). A 50% response rate using docetaxel 35 to 40 mg/m2/wk has been achieved in patients with metastatic breast cancer. When used concurrently with radiation therapy, weekly scheduling allowed a maximization of docetaxel dosing, with the maximum tolerated dose being 20 mg/m2/wk. It is likely that this novel schedule of docetaxel will allow the drug to be used with decreased toxicity and will facilitate its incorporation into active combination regimens. Further investigation of this novel schedule of administration is warranted.
多西他赛(泰索帝;法国安托尼罗纳-普朗克-罗瑞公司)是一种高效的抗肿瘤药物;然而,每3周给药一次会产生严重的骨髓抑制。基于最近的观察结果,即每周给药紫杉醇可将骨髓抑制降至最低,已开始对每周给药多西他赛进行研究。最近完成的一项多西他赛每周给药的I期研究表明,采用这种给药方案骨髓抑制明显减轻。最大耐受剂量为43mg/m²/周;采用此剂量时,骨髓抑制较轻,剂量限制性毒性为疲劳/乏力。当给药剂量低于40mg/m²/周时,其他非血液学毒性并不常见。尽管地塞米松给药方案缩短(在多西他赛给药前12小时开始,每12小时8mg,共三剂),但未观察到水肿。转移性乳腺癌患者使用35至40mg/m²/周的多西他赛实现了50%的缓解率。与放射治疗同时使用时,每周给药方案可使多西他赛剂量最大化,最大耐受剂量为20mg/m²/周。这种多西他赛的新给药方案可能会使该药物在毒性降低的情况下使用,并有助于将其纳入有效的联合治疗方案中。有必要对这种新的给药方案进行进一步研究。