Potential clinical applications of epothilones: a review of phase II studies
Potential clinical applications of epothilones: a review of phase II studies
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DOI：
10.1093/annonc/mdm176
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发表时间：
2007-01-01
影响因子：
50.5
通讯作者：
Kaye, S. B.
中科院分区：
文献类型：
--
作者：
Larkin, J. M. G.;Kaye, S. B.
背景：Epothilone是一种细胞毒性大环内酯类化合物，其作用机制与紫杉烷相似，但在紫杉烷耐药环境中表现出抗肿瘤活性。设计：这篇综述总结了11期临床研究的数据，分别是埃克沙比平(bms-247550)、帕托皮龙(epo-906)和kos-862。通过检索PubMed以及美国临床肿瘤学会年会和欧洲癌症学会联合会2000-2006年两年一度的会议记录来确定数据。结果：在II期研究中，埃泊硫酮在肺癌、卵巢癌、乳腺癌、前列腺癌和肾癌以及非霍奇金淋巴瘤中均表现出活性。在其他肿瘤类型的研究中，很少或没有临床活性的证据报道。初步数据表明，环磷酰胺类药物可以安全地与卡铂等其他细胞毒剂联合使用。结论：如果在耐药环境中的活性能够得到证实，并且具有可接受的毒性分布，则环磷酰胺类药物可以作为紫杉烷类药物的替代品。目前还在等待随机研究，以调查埃博西酮在单药和联合用药方案中的应用。
Background: Epothilones are cytotoxic macrolides that share a similar mechanism of action with the taxanes but demonstrate antitumor activity in taxane-resistant settings. Six epothilones are in early clinical trials for cancer treatment.Design: This review summarizes data from phase 11 clinical studies of the epothilones ixabepilone (BMS-247550), patupilone (EPO906), and KOS-862. Data were identified by searches of PubMed and of the proceedings of the American Society of Clinical Oncology annual meetings and the Federation of European Cancer Societies biennial conference for the period 2000-2006. Studies were included if safety and efficacy data were available for at least 10 patients with a given tumor type in a standard phase II design.Results: Epothilones have demonstrated activity in lung, ovarian, breast, prostate, and renal carcinomas and in non-Hodgkin's lymphoma in phase II studies. Little or no evidence of clinical activity has been reported in studies of epothilones in other tumor types. Preliminary data indicate that epothilones can be combined safely with other cytotoxic agents such as carboplatin.Conclusions: The epothilones may play a role as an alternative to taxanes if activity in resistant settings can be confirmed together with an acceptable toxicity profile. Randomized studies are awaited to investigate the utility of epothilones in single-agent and combination regimens.