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紫杉醇:紫杉烷类中的首个药物,是一类重要的新型抗肿瘤药物。

Taxol: the first of the taxanes, an important new class of antitumor agents.

作者信息

Rowinsky E K, Onetto N, Canetta R M, Arbuck S G

机构信息

Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Center, Baltimore, MD 21205.

出版信息

Semin Oncol. 1992 Dec;19(6):646-62.

PMID:1361079
Abstract

The taxanes represent the first class of antimicrotubule agents with a new mechanism of cytotoxic action since the introduction of the vinca alkaloids several decades ago. These compounds may prove to be the "anticancer drugs of the 1990s," just as the anthracyclines and the platinum compounds were the "anticancer drugs" of the 1970s and 1980s. Like the platinums, taxol, the prototypic taxane, has shown significant antineoplastic activity in patients with advanced ovarian cancer, with response rates ranging from 20% to 50%. Moreover, taxol has been shown to be useful in patients with platinum-resistant ovarian cancer. Although phase II screening is not yet complete, the results of phase II studies of taxol in advanced cancers of the ovary, breast (response rates, 56% to 62%), and lung (response rates, 21% to 24%) have rekindled interest in the microtubule as a prime strategic target for cancer therapy. After briefly reviewing the mechanisms of antineoplastic action and resistance and the results of preliminary clinical and pharmacological studies, this review will discuss several critical issues that will be addressed in future clinical trials, developmental directions, and drug supply. Although this review will focus primarily on taxol, the results of preliminary investigations with the semisynthetic taxane analog taxotere will also be discussed.

摘要

自几十年前引入长春花生物碱以来,紫杉烷类是具有新细胞毒性作用机制的第一类抗微管药物。这些化合物可能会成为“20世纪90年代的抗癌药物”,就像蒽环类药物和铂类化合物是20世纪70年代和80年代的“抗癌药物”一样。与铂类药物类似,原型紫杉烷类药物紫杉醇在晚期卵巢癌患者中显示出显著的抗肿瘤活性,缓解率在20%至50%之间。此外,紫杉醇已被证明对铂耐药的卵巢癌患者有用。尽管II期筛查尚未完成,但紫杉醇在晚期卵巢癌、乳腺癌(缓解率为56%至62%)和肺癌(缓解率为21%至24%)的II期研究结果重新激发了人们将微管作为癌症治疗主要战略靶点的兴趣。在简要回顾抗肿瘤作用和耐药机制以及初步临床和药理学研究结果后,本综述将讨论未来临床试验、研发方向和药物供应中将要解决的几个关键问题。尽管本综述将主要关注紫杉醇,但也将讨论半合成紫杉烷类似物多西他赛的初步研究结果。

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