Current status and future prospects for satraplatin, an oral platinum analogue
Current status and future prospects for satraplatin, an oral platinum analogue
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DOI：
10.1158/1078-0432.ccr-07-2176
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发表时间：
2008-03-15
影响因子：
11.5
通讯作者：
Yao, Min
中科院分区：
文献类型：
--
作者：
Choy, Hak;Park, Clinton;Yao, Min
铂类药物是主要的化疗药物，在许多人类恶性肿瘤的治疗中单独使用或与其他全身药物和/或放射治疗联合使用。美国食品和药物管理局批准的顺铂、卡铂和奥沙利铂这三种铂类药物都是静脉给药。沙特铂是第一个正在积极临床研究的口服铂类药物。沙特铂及其主要代谢物JM118已经在体外、体内和临床环境中显示出抗肿瘤活性。使用沙特铂作为替代铂类细胞毒性药物特别有吸引力，因为给药方便，毒性较轻，与顺铂缺乏交叉耐药，作为放射增敏剂的理论优势，以及对铂类药物无反应的癌症的活性。萨特铂最成熟的临床数据来自最近完成的III期试验，该试验调查了萨特铂和泼尼松对激素难治性前列腺癌患者的疗效，这些患者接受了一个疗程的其他化疗药物。初步报告显示，在无进展生存期、前列腺特异性抗原反应、客观肿瘤反应、疼痛反应和疼痛反应持续时间等多个终点上，联合用药在统计学上优于安慰剂和泼尼松。然而，总生存率的差异没有达到统计学意义。
Platinum drugs are major chemotherapeutic agents that are used alone or in combination with other systemic agents and/or radiation therapy in the management of many human malignancies. All three platinum drugs approved by the Food and Drug Administration, cisplatin, carboplatin, and oxaliplatin, are administrated intravenously. Satraplatin is the first orally administered platinum drug under active clinical investigation. Satraplatin and its major metabolite, JM118, have shown antineoplastic activity in in vitro, in vivo, and in clinical settings, Use of satraplatin as an alternative platinum cytotoxic agent is particularly attractive because of the convenience of administration, milder toxicity profile, lack of cross-resistance with cisplatin, theoretical advantage as a radiosensitizer, and activity in cancers historically nonresponsive to platinum drugs. The most mature clinical data for satraplatin come from the recently completed phase III trial that investigated the efficacy of satraplatin and prednisone on hormone-refractory prostate cancer patients who had failed a course of other chemotherapy agents. Preliminary reports show that the combination is statistically superior to placebo and prednisone in multiple end points, including progression-free survival, prostate-specific antigen response, objective tumor response, pain response, and duration of pain response. The difference in overall survival, however, did not reach statistical significance.