Pharmacy Department, Hospital De La Santa Creu I Sant Pau, Barcelona, Spain.
U705, Isciii Center for Biomedical Research on Rare Diseases (Ciberer), Barcelona, Spain.
Expert Opin Drug Metab Toxicol. 2021 Oct;17(10):1157-1163. doi: 10.1080/17425255.2021.1974397. Epub 2021 Sep 6.
Irinotecan is a cytotoxic agent that is widely used in the treatment of several types of solid tumors. However, although it is generally well tolerated, approximately 20% to 35% of patients develop severe toxicity, particularly delayed-type diarrhea and neutropenia. As the incidence of such toxicities is often associated with the and genotypes, individualized dosing could reduce these adverse events. Furthermore, prospective trials have shown that patients harboring the and genotypes can tolerate higher doses of irinotecan, which may in turn impact on a better outcome. Upfront genotyping could therefore be a usefulness strategy in order to individualize irinotecan dosing, but consensus on the recommended dose based on the genotype is still lacking.
This review summarizes the results of the main pharmacogenetic studies focused on irinotecan. We provide an overview of current evidence and recommendations for individualized dosing of irinotecan in metastatic colorectal cancer patients.
Implementation of and genotyping in clinical practice is a first step toward personalizing irinotecan therapy. This approach is likely to improve patient care and reduce healthcare costs. Future large and prospective studies will help to clarify the clinical value of other genetic markers in irinotecan treatment personalization.
伊立替康是一种细胞毒性药物，广泛用于治疗多种实体瘤。然而，尽管其一般耐受性良好，但约 20%至 35%的患者出现严重毒性，特别是迟发性腹泻和中性粒细胞减少症。由于这些毒性的发生频率通常与 和 基因型有关，个体化剂量可能会降低这些不良反应。此外，前瞻性试验表明，携带 和 基因型的患者可以耐受更高剂量的伊立替康，这可能会影响更好的结果。因此， upfront 基因型检测可能是一种有用的策略，可以实现伊立替康的个体化剂量，但基于 基因型推荐的剂量仍缺乏共识。
本文综述了主要的以伊立替康为重点的药物遗传学研究结果。我们概述了目前在转移性结直肠癌患者中个体化伊立替康剂量的证据和建议。
在临床实践中实施 和 基因型检测是实现伊立替康个体化治疗的第一步。这种方法有望改善患者的护理并降低医疗保健成本。未来的大型前瞻性研究将有助于阐明其他遗传标记在伊立替康治疗个体化中的临床价值。
