Peng Ling, Ye Xianghua, Zhou Yun, Zhang Junyan, Zhao Qiong
Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Support Care Cancer. 2015 Sep;23(9):2813-24. doi: 10.1007/s00520-015-2648-2. Epub 2015 Feb 13.
Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo.
We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies.
Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib.
Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.
硼替佐米是一种蛋白酶体抑制剂，已显示出对复发或新诊断的多发性骨髓瘤（MM）和套细胞淋巴瘤具有活性。虽然使用该药物后周围神经病变已有报道，但其总体发生率和相对风险仍不明确。我们进行了一项荟萃分析，以计算与静脉注射硼替佐米治疗MM和淋巴瘤相关的周围神经病变的发生率，并比较与安慰剂相比的相对风险。
我们检索了PubMed、Embase、Cochrane数据库以及美国临床肿瘤学会（ASCO）的会议记录，以查找相关临床试验。符合条件的研究包括关于MM和淋巴瘤患者静脉注射硼替佐米相关周围神经病变毒性特征的前瞻性2期和3期临床试验。根据纳入研究的异质性，采用固定效应或随机效应模型进行统计分析，以计算汇总发生率、相对风险（RRs）和95%置信区间（CIs）。
总共选择了34项临床试验进行荟萃分析，共纳入6492例患者。周围神经病变（所有级别）的发生率为33.9%（95%CI，29.9 - 38.5%），高级别事件的发生率为8.1%（95%CI，6.9 - 9.4%）。与安慰剂相比，硼替佐米诱导的周围神经病变的相对风险在所有级别（RR = 4.89；95%CI，2.52 - 9.51）和高级别（RR = 4.53；95%CI，2.04 - 10.07）周围神经病变中均增加（仅针对随机对照试验）。我们的分析还按不同基础疾病进行了分层，接受静脉注射硼替佐米治疗时，淋巴瘤患者所有级别周围神经病变的发生率高于MM患者。
静脉注射硼替佐米治疗与发生周围神经病变的风险增加相关。
