Emerging role of topotecan in front-line treatment of carcinoma of the ovary.
Emerging role of topotecan in front-line treatment of carcinoma of the ovary.
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DOI：
10.1634/theoncologist.7-suppl_5-46
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发表时间：
2002-10
期刊：
影响因子：
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通讯作者：
R. Coleman
中科院分区：
文献类型：
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作者：
R. Coleman
晚期上皮性卵巢癌的传统一线化疗策略是单独或与紫杉烷联合应用铂(卡铂和顺铂)。然而，在二线和挽救卵巢癌患者的II/III期试验中，已经确定了一些活性药物，这些药物可能会加强这一一线策略。一种名为Topotecan的药物在复发性卵巢癌患者中具有与紫杉醇相当的抗肿瘤活性，是二线或抢救环境中的既定治疗方法。此外，其作用机制不同于紫杉醇，是不重叠的。这些特性，再加上在肿瘤模型中观察到的拓扑替康、紫杉醇和铂之间的体外协同作用，为研究人员在卵巢癌一线治疗中检查拓扑替康提供了理论基础。正在积极研究将拓扑替康纳入一线治疗的若干策略，包括用拓扑替康取代紫杉醇，用顺铂或卡铂和紫杉醇进行三联疗法，先用几个疗程的铂剂和紫杉醇，然后再用几个疗程的拓扑替康的巩固方案，以及序贯双联疗法，即患者在每一个疗程中都接受铂，作为交替或顺序拓扑替康和紫杉醇双联方案的一部分。这些新方案正在进行的临床试验的初步数据显示，良好的应答率和一般可控的毒性情况。这篇综述总结了与这四种策略相关的初步临床结果，并概述了正在进行的和未来的拓扑替康治疗一线卵巢癌的随机研究。
The conventional front-line chemotherapy strategy for advanced epithelial ovarian carcinoma has become adjuvant administration of platinum (carboplatin and cisplatin), either alone or, most often, in combination with a taxane. However, a number of active agents have been identified in phase II/III trials of second-line and salvage ovarian cancer patients that may augment this front-line strategy. One agent, topotecan, has antitumor activity comparable with paclitaxel in patients with recurrent ovarian cancer and is an established treatment in second-line or salvage settings. Additionally, its mechanism of action is different from paclitaxel and is nonoverlapping. These properties, coupled with the in vitro synergy observed in tumor models among topotecan, paclitaxel, and platinum, have provided the rationale for investigators to examine topotecan in front-line ovarian cancer therapy. A number of strategies for incorporating topotecan into front-line therapy are under active investigation, including the replacement of paclitaxel with topotecan, a triplet regimen with cisplatin or carboplatin and paclitaxel, a consolidation regimen consisting of several courses of a platinum agent and paclitaxel followed by several courses of topotecan, and a sequential doublet regimen in which patients receive platinum in every course as part of a doublet with alternating or sequential topotecan and paclitaxel. Preliminary data from ongoing clinical trials of these new regimens show favorable response rates and generally manageable toxicity profiles. This review summarizes the preliminary clinical findings associated with the four strategies and outlines ongoing and future randomized studies of topotecan in front-line ovarian cancer.