Zagouri Flora, Sergentanis Theodoros N, Chrysikos Dimosthenis, Dimopoulos Meletios-Athanassios, Bamias Aristotle
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece.
First Propaedeutic Surgical Department, Hippokration Hospital, University of Athens, Athens, Greece.
Onco Targets Ther. 2015 Aug 20;8:2187-98. doi: 10.2147/OTT.S77342. eCollection 2015.
Ovarian cancer is the most lethal gynecologic malignancy; consequently, there is a need for effective therapies. Epothilones are microtubule-stabilizing agents that inhibit cell growth. Currently, patupilone and its four synthetic derivatives ixabepilone, BMS-310705, sagopilone, 20-desmethyl-20-methylsulfanyl epothilone B and epothilone D, as well as its derivative KOS-1584, are under clinical evaluation. This is the first systematic review conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines that synthesizes all available data emerging from trials and evaluates the efficacy and safety of epothilones in epithelial ovarian, primary fallopian tube, and primary peritoneal cancer. Despite the fact that epothilones have proven active in taxane-resistant settings in preclinical models, it is not yet clear from Phase II/III studies reviewed here that their clinical activity is superior to that of taxanes. Nevertheless, responses to epothilones have been observed in platinum-refractory/resistant ovarian cancer patients. Moreover, despite the shared mechanism of action of epothilones, their clinical profile seems clearly different, with diarrhea being the most common dose-limiting toxicity encountered with patupilone, whereas neutropenia and sensory neuropathy are the most common toxic effects observed with the other epothilones. In any case, randomized trials comparing epothilones with standard treatments seem warranted to define further the role of these agents, whereas biomarker analysis might further optimize patient selection.
卵巢癌是最致命的妇科恶性肿瘤，因此需要有效的治疗方法。埃坡霉素是一类能抑制细胞生长的微管稳定剂。目前，帕妥珠利及其四种合成衍生物伊沙匹隆、BMS-310705、司马匹隆、20-去甲基-20-甲基硫烷基埃坡霉素B和埃坡霉素D，以及其衍生物KOS-1584正在进行临床评估。这是首次按照PRISMA（系统评价和Meta分析的首选报告项目）指南进行的系统评价，该评价综合了试验中出现的所有可用数据，并评估了埃坡霉素在上皮性卵巢癌、原发性输卵管癌和原发性腹膜癌中的疗效和安全性。尽管埃坡霉素在临床前模型的紫杉烷耐药环境中已被证明具有活性，但从这里回顾的II/III期研究中尚不清楚它们的临床活性是否优于紫杉烷。然而，在铂类难治/耐药的卵巢癌患者中已观察到对埃坡霉素的反应。此外，尽管埃坡霉素具有共同的作用机制，但其临床特征似乎明显不同，腹泻是帕妥珠利最常见的剂量限制性毒性，而中性粒细胞减少和感觉神经病变是其他埃坡霉素最常见的毒性作用。无论如何，将埃坡霉素与标准治疗进行比较的随机试验似乎有必要进一步明确这些药物的作用，而生物标志物分析可能会进一步优化患者选择。
