Seidman A D
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Ann Oncol. 1994;5 Suppl 6:S17-22.
The search for new active agents and strategies to improve the prognosis for patients with stage IV breast cancer has led to examination of paclitaxel. Several clinical trials have been undertaken to determine its optimal use and clarify its role in the treatment of breast cancer and other malignancies. Several phase II trials involving breast cancer patients with limited prior therapy have yielded overall response rates (complete response and partial response) of 44% to 62% among women receiving paclitaxel. Treatment was generally well tolerated, with febrile neutropenia the most common side effect. An interim analysis of the European-Canadian Randomized Trial in Metastatic Breast Cancer demonstrated safety and efficacy of paclitaxel in a multicenter setting. Among the 234 patients evaluable for response, 29% (34/117) responded at 175 mg/m2 paclitaxel and 22% responded (26/117) at 135 mg/m2. Treatment was well tolerated at both dose levels; responses continue to evolve in patients who remain on study. Among patients with extensive prior therapy (> 2 prior regimens for stage IV disease), paclitaxel also has demonstrated safety and efficacy. At Memorial Sloan-Kettering Cancer Center, responses were noted among 36% of patients who had received two prior treatments and 21% of those who had received 3 or more. Paclitaxel was administered at 200 mg/m2 plus G-CSF. Other studies involving heavily pretreated patients yielded overall response rates as high as 53%. The concerns about cross-resistance between paclitaxel and doxorubicin (or other agents for which resistance is thought to be at least partly due to P-glycoprotein-mediated pleiotropic drug resistance) also are addressed.
对新型活性药物及改善IV期乳腺癌患者预后策略的探索促使人们对紫杉醇展开研究。已开展多项临床试验以确定其最佳用法，并阐明其在乳腺癌及其他恶性肿瘤治疗中的作用。几项针对既往治疗有限的乳腺癌患者的II期试验显示，接受紫杉醇治疗的女性总体缓解率（完全缓解和部分缓解）为44%至62%。治疗一般耐受性良好，发热性中性粒细胞减少是最常见的副作用。一项欧洲-加拿大转移性乳腺癌随机试验的中期分析证明了紫杉醇在多中心环境中的安全性和有效性。在234例可评估缓解情况的患者中，接受175mg/m²紫杉醇治疗的患者中有29%（34/117）出现缓解，接受135mg/m²治疗的患者中有22%（26/117）出现缓解。两个剂量水平的治疗耐受性均良好；仍在研究中的患者的缓解情况仍在演变。在既往接受广泛治疗（IV期疾病既往治疗方案>2种）的患者中，紫杉醇也显示出安全性和有效性。在纪念斯隆凯特琳癌症中心，接受过两种既往治疗的患者中有36%出现缓解，接受过3种或更多既往治疗的患者中有21%出现缓解。紫杉醇的给药剂量为200mg/m²加粒细胞集落刺激因子。其他涉及高度预处理患者的研究总体缓解率高达53%。还探讨了对紫杉醇与阿霉素（或其他认为耐药至少部分归因于P-糖蛋白介导的多药耐药的药物）之间交叉耐药的担忧。
