Taxanes in hormone-refractory prostate cancer.
Taxanes in hormone-refractory prostate cancer.
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激素难治性前列腺癌中的紫杉烷类药物。
DOI：
10.1046/j.1523-5394.1999.75005.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Dahut,W
中科院分区：
文献类型：
--
作者：
Kang,MH;Figg,WD;Dahut,W
将雌莫司汀与紫杉烷类化合物组合的基本原理是基于这样的假设，即使用与微管中不同但互补的蛋白质靶结合的药物可以实现对微管功能和细胞毒性的更大抑制。雌莫司汀和紫杉醇在体外对人雄激素非依赖性前列腺癌细胞系（DU 145）显示出协同的细胞毒性，其浓度低于临床上通常达到的浓度。Hudes和同事8临床评价了紫杉醇联合口服雌莫司汀治疗转移性HRPC患者的效果。进行了一项评价每日雌莫司汀和输注紫杉醇联合治疗的I期试验。8紫杉醇以120 mg/m2的剂量持续96小时联合雌莫司汀以600 mg/m2/d被发现是最大耐受剂量。65%的患者PSA水平下降50%或更多。2例可测量软组织转移的患者均获得客观缓解。未观察到4级毒性。在随后的II期试验中，34例患者接受紫杉醇，120 mg/m2，在每个21天周期的第1天至第4天96小时静脉输注，同时连续每日口服磷酸雌莫司汀，600 mg/m2/d。9在治疗前PSA水平升高的32例患者中，53%的患者PSA水平下降≥ 50%，28.1%的患者PSA水平下降≥ 80%。在9名患有可测量疾病的患者中，4名患者（44%）表现出客观缓解。估计中位生存期为7个月。最常见的毒副反应为中性粒细胞减少和厌食。
rationale for combining estramustine with taxanes was based on the hypothesis that greater inhibition of microtubule function and cytotoxicity could be achieved using drugs that bind to different, but complementary protein targets in the microtubule. Estramustine and paclitaxel demonstrated synergistic cytotoxicity in vitro in a human androgen-independent prostate carcinoma cell line (DU 145) at concentrations below those commonly achieved clinically.Hudes and colleagues8 clinically evaluated paclitaxel plus oral estramustine in patients with metastatic HRPC. A phase I trial evaluating the combination of daily estramustine and infusional paclitaxel was performed. 8 Paclitaxel at a dose of 120 mg/m2 over 96 hours combined with estramustine at 600 mg/m2/d was found to be the maximum tolerated dose. Sixty-five percent of patients had a PSA level decline of 50% or more. Both patients with measurable soft-tissue metastases had objective responses. No grade 4 toxicities were noted. In a subsequent phase II trial, thirtyfour patients received paclitaxel, 120 mg/m2, by 96-hour intravenous infusion on days 1 through 4 each 21-day cycle, together with continuous daily oral estramustine phosphate, 600 mg/m2/d. 9 Among the thirty-two patients with elevated pretreatment PSA levels, 53% had a decline of PSA level greater than or equal to 50%, and 28.1% had a greater than or equal to 80% decrease. Among nine patients with measurable disease, four patients (44%) showed objective responses. The estimated median survival time was 7 months. The most common toxicities were neutropenia and anorexia.