Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Eur J Cancer. 2019 Jul;115:111-119. doi: 10.1016/j.ejca.2019.04.023. Epub 2019 May 24.
Chemotherapy-induced peripheral neuropathy (CIPN) is a significant and debilitating side effect. However, there have been no studies of the relative risk of CIPN with known causative agents. We examined the risk of CIPN in patients taking such agents as a part of the National Cancer Institute (NCI) Cancer Therapy Evaluation Program-sponsored phase I trials.
CIPN events in each patient were graded according to the Clinical Terminology of Common Adverse Effects and compared among several high-risk chemotherapeutic agent groups, adjusting for possible confounding factors. Patients receiving tubulin-targeted agents were analysed separately for specific background factors associated with CIPN.
In 135 phase I clinical trials, 259 of 3614 patients were identified as developing CIPN during chemotherapy. Tubulin-targeting agents and proteasome inhibitors were identified as high-risk agents (hazard ratio 9.04 and 5.01, respectively) for CIPN, whereas platinum-complex agents and thalidomide analogues imparted lower risk (hazard ratio 1.52 and 1.11, respectively). Age, sex and medical history of diabetes were not significantly related to CIPN. CIPN developed over time as the number of chemotherapy cycles increased. Among patients with CIPN, treatment with tubulin-targeting agents resulted in a significantly higher rate of chemotherapy schedule modification compared with treatments with other chemotherapeutic agents.
Tubulin-targeting agents and proteasome inhibitors were associated with a greatly increased risk of CIPN compared with other agents. CIPN tended to develop in later chemotherapy cycles. These findings will help to minimise the risk of CIPN by encouraging increased surveillance and earlier dose adjustment of high-risk agents in phase I trials.
化疗引起的周围神经病（CIPN）是一种严重且使人虚弱的副作用。然而，目前还没有研究过已知致病药物引起 CIPN 的相对风险。我们研究了接受国家癌症研究所（NCI）癌症治疗评估计划赞助的 I 期试验中这些药物的患者发生 CIPN 的风险。
根据常见不良反应临床术语对每位患者的 CIPN 事件进行分级，并在调整可能的混杂因素后，比较几种高风险化疗药物组之间的 CIPN 风险。对于与 CIPN 相关的特定背景因素，分别分析接受微管靶向药物治疗的患者。
在 135 项 I 期临床试验中，3614 名患者中有 259 名在化疗期间被确定为患有 CIPN。微管靶向药物和蛋白酶体抑制剂被确定为 CIPN 的高风险药物（危险比分别为 9.04 和 5.01），而铂类药物和沙利度胺类似物的风险较低（危险比分别为 1.52 和 1.11）。年龄、性别和糖尿病病史与 CIPN 无显著相关性。随着化疗周期数的增加，CIPN 逐渐发展。在患有 CIPN 的患者中，与接受其他化疗药物治疗的患者相比，接受微管靶向药物治疗的患者化疗方案修改率显著更高。
与其他药物相比，微管靶向药物和蛋白酶体抑制剂与 CIPN 的风险显著增加相关。CIPN 往往在后期化疗周期中发展。这些发现将有助于通过鼓励增加对 I 期试验中高风险药物的监测和更早的剂量调整，最大程度地降低 CIPN 的风险。
