Pemetrexed (Alimta): a novel multitargeted antifolate agent.
Pemetrexed (Alimta): a novel multitargeted antifolate agent.
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DOI：
10.1586/14737140.3.2.145
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发表时间：
2003-04-01
影响因子：
3.3
通讯作者：
Adjei, Alex A
中科院分区：
文献类型：
--
作者：
Adjei, Alex A
培美曲塞（Alimta）是一种新型多靶点抗叶酸剂，可抑制至少三种参与叶酸代谢以及嘌呤和嘧啶合成的酶。这些酶是胸苷酸合成酶、二氢叶酸还原酶和甘氨酰胺核糖核苷酸甲酰转移酶。培美曲塞在II期临床试验中显示出广泛的抗肿瘤活性，用于治疗各种实体瘤，包括间皮瘤、非小细胞肺癌、乳腺癌、宫颈癌、结直肠癌、头颈癌和膀胱癌。当培美曲塞与顺铂和吉西他滨（健择）联合使用时，也证明了有希望的活性。一个关键的III期研究间皮瘤已提交。本研究表明，培美曲塞联合顺铂与顺铂单药治疗该疾病相比具有优效性。培美曲塞最显著的毒性、骨髓抑制和粘膜炎已通过补充叶酸和维生素B12得到显著改善。更重要的是，维生素补充剂没有表现出任何不良疗效。本文综述了培美曲塞的生物化学和临床活性。
Pemetrexed (Alimta) is a novel, multitargeted antifolate that inhibits at least three of the enzymes involved in folate metabolism, and purine and pyrimidine synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated broad antitumor activity in Phase II trials in a wide variety of solid tumors, including mesothelioma, non-small cell lung, breast, cervical, colorectal, head and neck, and bladder cancers. Promising activity has also been demonstrated when pemetrexed is combined with cisplatin and gemcitabine (Gemzar). A pivotal Phase III study in mesothelioma has been presented. This study indicates the superiority of pemetrexed in combination with cisplatin versus cisplatin alone in this disease. The most significant toxicities of pemetrexed, myelosuppression and mucositis have been significantly ameliorated by folate and vitamin B12 supplementation. More importantly, vitamin supplementation has not demonstrated any adverse efficacy. This review discusses the biochemistry and clinical activity of pemetrexed.