IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Lung Cancer Unit, Genova, Italy.
Expert Opin Pharmacother. 2013 Aug;14(11):1545-58. doi: 10.1517/14656566.2013.802774. Epub 2013 May 17.
Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. Although advanced NSCLC is still incurable, various anti-neoplastic agents have become available for the treatment of this disease. Pemetrexed , a multi-target folate antagonist, has improved the survival of non-squamous NSCLC patients. Currently, pemetrexed is approved for first-line treatment in combination with a platinum derivate, for second-line treatment as a single agent and, more recently, as maintenance treatment after first-line chemotherapy.
The authors analyzed the state of the art of pemetrexed through a review of the literature. Clinical trials and meta-analyses involving pemetrexed in NSCLC were evaluated. Pemetrexed improved survival of non-squamous NSCLC in first-line, maintenance, and second-line treatments; this benefit is limited to non-squamous histology. Because pemetrexed has become part of the standard of care, current clinical trials are designed to compare it to other investigational combinations. Limited data on resectable disease are available, and additional clinical trials are being conducted.
Pemetrexed has shown effectiveness and a favorable toxicity profile. Histology-driven indications and the relationship of pemetrexed with thymidylate synthase expression suggest that a more precise definition of predictive biomarkers could be further investigated.
非小细胞肺癌(NSCLC)是全球癌症相关死亡的主要原因。尽管晚期 NSCLC 仍然无法治愈,但已有多种抗肿瘤药物可用于治疗这种疾病。培美曲塞是一种多靶点叶酸拮抗剂,可改善非鳞状 NSCLC 患者的生存。目前,培美曲塞已获准与铂类衍生物联合用于一线治疗,作为单一药物用于二线治疗,最近还可用于一线化疗后的维持治疗。
作者通过文献回顾分析了培美曲塞的最新技术状况。评估了涉及 NSCLC 中培美曲塞的临床试验和荟萃分析。培美曲塞在一线、维持和二线治疗中改善了非鳞状 NSCLC 的生存;这种获益仅限于非鳞状组织学。由于培美曲塞已成为标准治疗的一部分,目前的临床试验旨在将其与其他研究性联合治疗进行比较。关于可切除疾病的有限数据可用,并且正在进行额外的临床试验。
培美曲塞已显示出有效性和良好的毒性特征。基于组织学的适应证以及培美曲塞与胸苷酸合成酶表达的关系表明,可进一步研究更精确的预测生物标志物定义。