培美曲塞:多目标antifolate。

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罗林斯KD,林德利C

培美曲塞:多目标antifolate。

其他。2005年9月,27 (9):1343 - 82。

PubMed ID
16291410 (在PubMed
]
文摘

背景:美国食品和药物管理局批准了2004年2月培美曲塞治疗恶性胸膜间皮瘤患者(MPM)与顺铂在不可切除的疾病或手术治疗为谁不是一个选择。培美曲塞是第一剂治疗MPM的批准。2004年8月,培美曲塞被批准作为二线,单药治疗的局部晚期或转移性非小细胞肺癌(NSCLC)。目的:本文的目的是总结药理学,药物动力学,功效,和安全的培美曲塞和审查其现有和潜在的角色在治疗MPM,非小细胞肺癌等肿瘤的条件。方法:相关英文文献被发现通过搜索PubMed(1966 - 2004年12月),国际制药摘要和美国临床肿瘤学会学报》(1995年1月- 2必威国际app004年12月)。必威国际app搜索条件包括培美曲塞爱宁达,MTA,多目标antifolate, LY231514,间皮瘤,MPM,非小细胞肺癌、非小细胞肺癌、乳腺癌、胰腺癌。除了发表文献,摘要和海报在综述了国内外科学会议。结果:Myelosuppression培美曲塞的主要dose-limiting毒性在第一阶段的研究报道。识别之间的相关性差叶酸状态和多变量分析导致培美曲塞毒性增加补充叶酸和维生素B12的要求对患者在所有培美曲塞的研究中,导致培美曲塞指出降低毒性。一个多中心、随机III期试验的疗效相比培美曲塞联合顺铂与顺铂单独MPM的治疗。 Response rates were 41.3% in the pemetrexed/cisplatin combination and 16.7% with single-agent cisplatin (P < 0.001). The median survival time for the pemetrexed/cisplatin combination was significantly longer at 12.1 months versus 9.3 months for cisplatin alone (P = 0.02). One international, multicenter, randomized Phase III trial in patients with NSCLC compared single-agent pemetrexed versus docetaxel in patients previously treated with chemotherapy. Overall response rates (9.1% and 8.8%) and median survival (8.3 months and 7.9 months) did not differ between pemetrexed and docetaxel (P = 0.105 and P = 0.226, respectively). Hematologic adverse effects-grade 3/4 neutropenia (40.2% vs 5.3%; P < 0.001), febrile neutropenia (12.7% vs 1.9%; P < 0.001), and neutropenic infections (3.3% vs 0%; P = 0.004)-were significantly greater in the docetaxel-treated patients than in the pemetrexed-treated patients, as was alopecia (37.7% vs 6.4%; P < 0.001). Results of an international, multicenter Phase III trial of pemetrexed in combination with gemcitabine conducted in patients with pancreatic cancer indicate that the combination is no more efficacious than single-agent gemcitabine. Results in other disease states are still preliminary. CONCLUSIONS: Pemetrexed is a multitargeted antifolate that has demonstrated antitumor activity in various tumor types as a single agent and in combination with other chemotherapeutic agents. Efficacy for the treatment of MPM in combination with cisplatin has been demonstrated, and approval as a second-line agent in NSCLC was based on response rate as a surrogate end point for survival. The addition of folic acid and vitamin B12 supplementation markedly reduced.

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