Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a multitargeted antifolate that inhibits several folate-dependent enzymes that play roles in purine and pyrimidine synthesis. The principal toxicities of pemetrexed are neutropenia, diarrhea, nausea/vomiting, mucositis, and skin rash. These toxicities are more frequent in vitamin-deficient (folate and vitamin B 12 ) patients, and can be ameliorated by the co-administration of folate and vitamin B 12 . The use of prophylactic dexamethasone is also recommended to reduce the frequency of severe skin rash. Pemetrexed has significant single-agent activity in previously treated and untreated patients with non-small cell lung cancer (NSCLC). A recent phase III trial comparing pemetrexed with docetaxel in previously treated NSCLC patients showed equivalent efficacy with less bone marrow toxicity (eg, neutropenia) in the pemetrexed group. These results were pivotal in the approval of pemetrexed for the treatment of refractory NSCLC. Pemetrexed has been combined with the platinums (ie, cisplatin, carboplatin, and oxaliplatin) in NSCLC to yield clinical activity similar to that of other platinum-based doublets. A comparative phase III trial of cisplatin/pemetrexed against cisplatin/gemcitabine (Gemzar; Eli Lilly and Co) is under way. Pemetrexed has also been evaluated in combination with gemcitabine, and although the optimal dose and schedule of this combination has not been defined, clinical activity similar to other nonplatinum-based doublets has been observed. Preliminary evidence suggests that pemetrexed can be combined with thoracic radiation therapy, but more data are needed to evaluate the potential advantage(s) pemetrexed may have in this setting. Pemetrexed/platinum doublets also appear to possess activity in extensive stage small cell lung cancer. A phase II trial of single-agent pemetrexed is under way in both sensitive- and refractory-relapsed small cell lung cancer. Given the activity and excellent tolerability of pemetrexed, further studies in lung cancer are warranted.

中文翻译：

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培美曲塞（Alimta）在肺癌中的作用不断发展。

Pemetrexed（Alimta；美国印第安纳州印第安纳波利斯的礼来公司）是一种多靶点抗叶酸药物，可抑制几种在嘌呤和嘧啶合成中起作用的叶酸依赖性酶。培美曲塞的主要毒性是中性粒细胞减少，腹泻，恶心/呕吐，粘膜炎和皮疹。这些毒性在维生素缺乏症（叶酸和维生素B 12）患者中更为常见，并且可以通过叶酸和维生素B 12的共同使用来缓解。还建议使用地塞米松预防剂，以减少严重皮疹的发生。培美曲塞在先前治疗和未治疗的非小细胞肺癌（NSCLC）患者中具有显着的单药活性。最近一项在先前治疗的NSCLC患者中比较培美曲塞与多西他赛的III期试验显示，培美曲塞组的等效疗效相同，但骨髓毒性（如中性粒细胞减少）较少。这些结果对于批准培美曲塞治疗难治性非小细胞肺癌至关重要。培美曲塞已与NSCLC中的铂类药物（即顺铂，卡铂和奥沙利铂）结合使用，产生的临床活性与其他铂类双线药物相似。一项针对顺铂/培美曲塞的顺铂/吉西他滨的对比III期试验（Gemzar；礼来公司）正在进行中。培美曲塞也已与吉西他滨联用进行了评估，尽管尚未确定该联合用药的最佳剂量和时间表，但已观察到与其他非铂类双联药物相似的临床活性。初步证据表明，培美曲塞可以与胸腔放疗结合使用，但是还需要更多数据来评估培美曲塞在这种情况下可能具有的潜在优势。培美曲塞/铂双合子在广泛期小细胞肺癌中似乎也具有活性。敏感性和难治性复发小细胞肺癌均已开始进行单药培美曲塞的II期临床试验。鉴于培美曲塞的活性和极好的耐受性，有必要对肺癌进行进一步的研究。培美曲塞单药的II期试验正在进行中，用于敏感性和难治性复发小细胞肺癌。鉴于培美曲塞的活性和极好的耐受性，有必要对肺癌进行进一步的研究。敏感性和难治性复发小细胞肺癌均已开始进行单药培美曲塞的II期临床试验。鉴于培美曲塞的活性和极好的耐受性，有必要对肺癌进行进一步的研究。