Morris Patrick G, Fornier Monica N
Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Clin Adv Hematol Oncol. 2009 Feb;7(2):115-22.
Taxanes, derived from the bark of the Pacific yew tree, were the last major group of cytotoxic agents to be developed. Their proven efficacy in a variety of malignancies has constituted a real breakthrough in the treatment of cancer. Wider clinical use of taxanes has several important limitations, including acquired and intrinsic tumor resistance, hypersensitivity reactions, and cumulative neurotoxicity and hematopoietic toxicity. Epothilones, naturally occurring macrolide antibiotics that also act on the microtubule, are a novel class of compounds that may circumvent some of these problems. Many synthetic and semisynthetic epothilone analogs have been formulated and have undergone varying degrees of testing. These compounds have demonstrated activity in a variety of tumors, including in tumors and cell lines resistant to taxanes. So far only ixabepilone has been tested in phase II and III trials and licensed by the US Food and Drug Administration for the treatment of metastatic breast cancer. The main dose-limiting toxicity appears to be a sensory peripheral neuropathy, as commonly seen with drugs that act on the microtubule. Further clinical studies assessing the role of ixabepilone in other settings, as well as the clinical investigation of other epothilones, are eagerly awaited.
紫杉烷类药物源自太平洋紫杉树的树皮，是最后一批研发的主要细胞毒性药物。它们在多种恶性肿瘤中已证实的疗效构成了癌症治疗方面的一项重大突破。紫杉烷类药物在临床上更广泛的应用存在几个重要局限性，包括获得性和内在性肿瘤耐药性、过敏反应以及累积性神经毒性和造血毒性。埃坡霉素是一类天然存在的大环内酯类抗生素，也作用于微管，是一类可能规避其中一些问题的新型化合物。许多合成和半合成的埃坡霉素类似物已被研制出来，并经过了不同程度的测试。这些化合物在多种肿瘤中都显示出活性，包括对紫杉烷类耐药的肿瘤和细胞系。到目前为止，只有伊沙匹隆进行了II期和III期试验，并获得美国食品药品监督管理局批准用于治疗转移性乳腺癌。主要的剂量限制性毒性似乎是感觉性周围神经病变，这与作用于微管的药物常见的情况一样。人们急切期待着进一步评估伊沙匹隆在其他情况下作用的临床研究，以及对其他埃坡霉素的临床研究。
