Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC.
JCO Oncol Pract. 2022 Apr;18(4):270-277. doi: 10.1200/OP.21.00624. Epub 2021 Dec 3.
Irinotecan is an anticancer agent widely used for the treatment of solid tumors, including colorectal and pancreatic cancers. Severe neutropenia and diarrhea are common dose-limiting toxicities of irinotecan-based therapy, and polymorphisms are one of the major risk factors of these toxicities. In 2005, the US Food and Drug Administration revised the drug label to indicate that patients with homozygous genotype should receive a decreased dose of irinotecan. However, testing is not routinely used in the clinic, and specific reasons include lack of access to concise information on this wide issue as well as mixed recommendations by regulatory and professional entities. To assist oncologists in assessing whether and when to use genetic testing in patients receiving irinotecan-based therapies, this article provided (1) essential knowledge of polymorphisms; (2) an update on the impact of polymorphisms on efficacy and toxicity of contemporary irinotecan-based regimens; (3) dosing adjustments based upon the genotypes, and (4) recommendations from currently available guidelines from the US and international scientific consortia and major oncology societies.
伊立替康是一种广泛用于治疗实体瘤(包括结直肠癌和胰腺癌)的抗癌药物。严重中性粒细胞减少和腹泻是伊立替康为基础的治疗的常见剂量限制毒性,而 多态性是这些毒性的主要危险因素之一。2005 年,美国食品和药物管理局修订了药物标签,表明纯合基因型的患者应接受伊立替康的减少剂量。然而,检测在临床上并未常规使用,具体原因包括缺乏有关这一广泛问题的简明信息,以及监管和专业实体的建议不一致。为了帮助肿瘤学家评估在接受伊立替康为基础的治疗的患者中是否以及何时使用 基因检测,本文提供了(1) 多态性的基本知识;(2) 多态性对当代伊立替康为基础的方案疗效和毒性的影响的最新信息;(3) 基于 基因型的剂量调整;以及(4) 来自美国和国际科学联盟以及主要肿瘤学会的现有指南的建议。