title: Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.
authors: Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors: Ling
authors: L
authors: Peng
authors: Xianghua
authors: X
authors: Ye
authors: Yun
authors: Y
authors: Zhou
authors: Junyan
authors: J
authors: Zhang
authors: Qiong
authors: Q
authors: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069286:Bortezomib / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D009101:Multiple Myeloma / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D010919:Placebos / Q000009:adverse effects; D011446:Prospective Studies; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D010919:Placebos; D000069286:Bortezomib