The status of platinum anticancer drugs in the clinic and in clinical trials
The status of platinum anticancer drugs in the clinic and in clinical trials
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DOI：
10.1039/c0dt00292e
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Oun, Rabbab
中科院分区：
文献类型：
--
作者：
Wheate, Nial J.;Walker, Shonagh;Oun, Rabbab
自1979年批准以来，顺铂已成为治疗卵巢癌、睾丸癌、肺癌和膀胱癌以及淋巴瘤、骨髓瘤和黑色素瘤的化疗方案的重要组成部分。不幸的是，它的持续使用受到严重的剂量限制性副作用和内在或获得性耐药性的极大限制。在过去的30年里，其他23种铂类药物已进入临床试验，其中只有两种（卡铂和奥沙利铂）获得国际上市批准，另外三种（奈达铂，洛铂和七铂）在个别国家获得批准。在此期间，失败的药物多于成功的药物，14种药物的开发在临床试验期间被停止。目前有四种药物处于临床试验的各个阶段（沙铂、吡铂、Lipoplatin（TM）和ProLindac（TM））。自1999年以来，没有新的小分子铂药物进入临床试验，这代表了过去十年中焦点从药物设计转向药物递送。在这篇前瞻性文章中，我们更新了目前批准使用的铂类抗癌药物的状态，正在进行临床试验的药物和在临床试验期间停止使用的药物，并在我们认为该领域将在未来十年发展的背景下讨论结果。
Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin (TM) and ProLindac (TM)). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.