Zhou Li-Yan, Shi Ye-Hui, Jia Yong-Sheng, Tong Zhong-Sheng
Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Chronic Dis Transl Med. 2015 Mar 23;1(1):27-35. doi: 10.1016/j.cdtm.2015.02.008. eCollection 2015 Mar.
This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens.
PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ''pemetrexed'' or ''LY231514'' or "Alimta", "metastatic breast cancer", and "advanced breast cancer".
There were 15 studies ( = 1002) meeting our criteria for evaluation. Eight single-agent trials ( = 551) and seven using combinations with other agents ( = 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer.
Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists.
本文综述培美曲塞在转移性乳腺癌患者中的药理学、药代动力学特性、临床疗效及安全性，以及基于培美曲塞方案治疗结局的预测生物标志物。
检索PubMed、Embase、OVID和Cochrane图书馆数据库，检索起始时间为各数据库建库之初，对发表日期无任何限制。检索词为“培美曲塞”或“LY231514”或“力比泰”、“转移性乳腺癌”和“晚期乳腺癌”。
有15项研究（n = 1002）符合我们的评估标准。确定了8项单药试验（n = 551）和7项与其他药物联合使用的试验（n = 451），这些试验评估了培美曲塞在转移性乳腺癌患者中的应用。培美曲塞单药治疗的缓解率在8%至31%之间，联合治疗的缓解率据报道在15.8%至55.7%之间。通过对患者常规补充叶酸、地塞米松和维生素B，这些患者的毒性反应较轻，包括剂量限制性中性粒细胞减少和血小板减少，以及较低级别的可逆性肝毒性和胃肠道毒性。胸苷酸合成酶（TS）和其他生物标志物的表达与乳腺癌患者对培美曲塞的预后和敏感性相关。
培美曲塞在治疗转移性乳腺癌患者方面显示出显著活性且毒性可接受。对培美曲塞在乳腺癌中的转化研究确定了生物标志物以及对其临床活性和毒性重要的其他基因。需要进一步研究以阐明培美曲塞在乳腺癌治疗中的作用，从而为肿瘤学家提供指导。
