摘要
卡非佐米在2012年被美国FDA批准成为治疗多发性骨髓瘤的新药后,随即成为了多发性骨髓瘤患者的一种新选择。但是关于卡非佐米及其组合物在治疗多发性骨髓瘤的临床效果没有很好的结论,因此我们收集现有的临床试验报告分析卡非佐米在临床应用上的效果,更好的说明该药的安全性与有效性,并试图寻求卡非佐米更佳的治疗方案。检索数据库包括cochrane、EMBASE、PubMed、Medline、中国知识资源总库CNKI、万方数据库等国内外数据库;检索关键字为:"Carfilzomib","Multiple myeloma","bortezomib","卡非佐米","多发性骨髓瘤"和"硼替佐米"。最后应用R软件对收集到的数据进行META分析,根据文章间的异质性决定使用固定效应模型或者随机效应模型。我们总共收集到了符合标准的文献总共17篇,总计1960名多发性骨髓瘤患者参与试验。卡非佐米单药使用临床试验中总计多发性骨髓瘤患者594名,总缓解率为32%(I^2=84.9%,P<0.0001);在10组卡非佐米联合使用的临床试验共计1366名多发性骨髓瘤患者,其中有1081名患者的治疗效果至少达到了PR(部分缓解),总缓解率为79%(I^2=91.0%,P<0.0001)。不良反应多为发热、恶心、呕吐等非血液学事件,其中周围神经性病变的发生率较硼替佐米有明显的改善。我们发现卡非佐米较硼替佐米耐受性好,其周围神经病变发生概率较小,治疗效果好,不受其他药物的影响。在本次分析中得出,卡非佐米,来那度胺和地塞米松联合使用的总缓解率最高,卡非佐米单药使用总缓解率较差且不良反应发生率较多。由此使用卡非佐米,来那度胺和地塞米松组合物作为治疗药物有较满意的临床效果,但不过该结论尚待将来更多实验数据的支持。
Carfilzomib has become a new choice for patients with multiple myeloma（MM）.However, the use of carfilzomib single-agent or in combination with other agents in MM patients is not explicitly clarified in clinical practice. Therefore, we analyzed the effects of carfilzomib and its safety and effectiveness using available clinical trial reports in order to find out the best therapy of carfilzomib. We searched MEDLINE, Embase, Pub Med and Cochrane databases as well as Chinese databases of carfilzomib trials（Jan. 2012 to Sep. 2016） for the MM treatment. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as the overall response rate（ORR） and performed by R software. A fixed-effects model or random-effects model was applied based on the heterogeneity among studies. Based on our research standard, we identified 17 prospective studies enrolling 1960 patients.A total of 594 MM patients were enrolled in carfilzomib single-agent clinical trials, and the ORR was 32%（I^2 = 84.9%, P〈0.0001）.A total of 1366 MM patients were enrolled in clinical trials of 10 groups of carfilzomib combination regimens, 1081 patients had a therapeutic effect, and the ORR was79%（I^2 = 91.0%, P〈0.0001）. The most frequent adverse events were fever, nausea, vomiting and other non-hematologic events. Carfilzomib was better tolerated than bortezomib, with a lower incidence of peripheral neuropathy and better therapeutic effects compared with other drugs. In this analysis, the highest ORR was achieved from combination of carfilzomib, lenalidomide and dexamethasone, which had a lower incidence of adverse events and a greater ORR compared with carfilzomib single-agent. Therefore, the combination of carfilzomib, lenalidomide and dexamethasone could be a good therapeutic agent with strong clinical effect. However, this conclusion needs to be validated in future study.
基金
Zhejiang Public Welfare Technology Application Research Project(Grant No.2015C33285)
Zhejiang Provincial Natural Science Foundation Project(Grant No.Y14H300005)
