抗肿瘤新药pemetrexed治疗乳腺癌的研究

pemetrexed是一种新型抗叶酸药,能够抑制叶酸代谢途径中的多种酶,从而抑制嘧啶和嘌呤生物的合成,达到抑制肿瘤的作用.Ⅱ期临床结果显示,pemetrexed单药对于初治和复治的进展期乳腺癌均有较高的疗效.毒副作用主要为中性粒细胞减少、食欲减退、乏力和皮疹.补充叶酸和Vit B12可显著减少pemetrexed的血液学毒性,预防性给予皮质激素可减轻皮疹的发生.

恶性胸膜间皮瘤诊治进展

恶性胸膜间皮瘤是一种进展性胸部恶性肿瘤.病因可能与石棉、SV40病毒和遗传倾向有关.诊断方法包括X线摄片、病理学和分子生物学检测.大多数恶性胸膜间皮瘤患者不能进行手术或放射治疗,细胞毒药物化疗剂成为唯一可选择的方法,有效率＜20%.近来一种多靶点抗叶酸剂pemetrexed,已进行了Ⅰ、Ⅱ、Ⅲ期临床试验并获得了可喜的结果.加用小剂量的叶酸和B12补充治疗能减轻pemetrexced的毒副反应.pemetrexed/顺铂以被推荐为恶性胸膜间皮瘤的一线化疗方案.

Objectives: 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. Methods: 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”. Results: There were 15 studies (n ? 1002) meeting our criteria for evaluation. Eight single-agent trials (n ? 551) and seven using combinations with other agents (n ? 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 B12, 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. Conclusion: 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. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Com-munications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).