Demurtas Sara, La Verde Nicla, Rota Selene, Casazza Giovanni, Montrasio Cristina, Cheli Stefania, Cona Maria Silvia, Dalu Davide, Fasola Cinzia, Ferrario Sabrina, Filipazzi Virginio, Gambaro Anna, Tosca Nicoletta, Clementi Emilio
Department of Oncology, Luigi Sacco University Hospital, ASST Fatebenefratelli-Sacco, Milan, Italy.
Department of Biomedical and Clinical Sciences "L. Sacco", Università degli Studi di Milano, Milan, Italy.
Pharmacogenomics J. 2021 Aug;21(4):491-497. doi: 10.1038/s41397-021-00227-7. Epub 2021 Mar 1.
Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A422 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C83/4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A422 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.
紫杉烷类药物用于治疗多种实体瘤。不良事件(AE)可能会受到负责药代动力学和药效学的蛋白质编码基因中的单核苷酸多态性(SNP)的影响。在这项前瞻性、单中心、观察性研究中,我们探讨了紫杉烷类药物代谢和转运相关主要基因中的SNP对125例接受紫杉醇、纳米白蛋白结合型紫杉醇或多西他赛治疗肿瘤的患者的毒性和疗效的影响。研究的SNP与不良事件之间无统计学显著关联。CYP3A422的杂合基因型在接受紫杉醇和纳米白蛋白结合型紫杉醇治疗的患者中显示出与皮肤反应的关联趋势(RR = 6.92;95%CI 0.47,99.8;p = 0.0766)。CYP2C83/4变异携带者在接受紫杉醇和纳米白蛋白结合型紫杉醇治疗的患者中显示出与总体不良事件的关联趋势(RR = 1.28;95%CI 0.96,1.67;p = 0.0898)。未发现与治疗疗效有统计学显著关系。ABCB1 3435TT显示出与更高治疗反应的关联趋势(RR = 0.22;95%CI 0.03,1.51;p = 0.0876)。尽管研究人群具有异质性,但CYP3A422和CYP2C8的SNP可能会影响紫杉醇和纳米白蛋白结合型紫杉醇的毒性,而ABCB1 c.3435可能会影响紫杉烷类药物的有效性,即使未发现任何统计学显著性。