Sigworth Elizabeth A, Rubinstein Samuel M, Chaugai Sandip, Rivera Donna R, Walker Philip D, Chen Qingxia, Warner Jeremy L
Department of Biostatistics, Vanderbilt University, Nashville, TN 37203, USA.
Division of Hematology, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
iScience. 2022 Mar 11;25(4):104045. doi: 10.1016/j.isci.2022.104045. eCollection 2022 Apr 15.
Members of the taxane class of chemotherapies, staples of cancer treatment since the 1990s, can induce chemotherapy-induced peripheral neuropathy (CIPN), a potentially irreversible outcome related to cumulative exposure. Switching between taxanes is often clinically necessary; however, different taxanes have different efficacies, toxicities, and dosing strategies, necessitating an evidence-based schema focused on toxicity. We performed a systematic review and meta-analysis of the literature on docetaxel and paclitaxel, extracting cumulative dose, rates of CIPN, and subject demographics, thereby establishing their dose-toxo-equivalence relationship through a Bayesian meta-analysis model, calculating doses of the two drugs that are expected to have comparable rates of CIPN, along with credible intervals. Our final model, based on 169 studies, produces credible interval widths that provide guidance within one treatment cycle. In practice, this model provides a framework under which oncologists can make treatment switching and dosing decisions, hopefully reducing patient risk of CIPN.
自20世纪90年代以来一直是癌症治疗主要手段的紫杉烷类化疗药物,可诱发化疗引起的周围神经病变(CIPN),这是一种与累积暴露相关的潜在不可逆后果。临床上常常需要在紫杉烷类药物之间进行切换;然而,不同的紫杉烷类药物具有不同的疗效、毒性和给药策略,因此需要一个以毒性为重点的循证方案。我们对多西他赛和紫杉醇的文献进行了系统评价和荟萃分析,提取了累积剂量、CIPN发生率和受试者人口统计学数据,从而通过贝叶斯荟萃分析模型建立它们的剂量-毒性等效关系,计算出预计CIPN发生率相当的两种药物的剂量以及可信区间。我们基于169项研究的最终模型产生的可信区间宽度可在一个治疗周期内提供指导。在实际应用中,该模型为肿瘤学家做出治疗切换和给药决策提供了一个框架,有望降低患者发生CIPN的风险。