Quaranta Sylvie, Thomas Fabienne
Service de pharmacocinétique et toxicologie, laboratoire de biologie médicale, hôpital de la Timone, Assistance publique-Hôpitaux de Marseille (AP-HM), 13005 Marseille, France.
Institut Claudius-Regaud, CRCT, Université de Toulouse, Inserm, UPS, 31059 Toulouse, France; GPCO-Unicancer, 101, rue de Tolbiac, 75013 Paris, France.
Therapie. 2017 Apr;72(2):205-215. doi: 10.1016/j.therap.2017.01.005. Epub 2017 Jan 30.
Individualized treatment is of special importance in oncology because the drugs used for chemotherapy have a very narrow therapeutic index. Pharmacogenetics may contribute substantially to clinical routine for optimizing cancer treatment to limit toxic effects while maintaining efficacy. This review presents the usefulness of pharmacogenetic tests for some key applications: dihydropyrimidine dehydrogenase (DPYD) genotyping for fluoropyrimidine (5-fluorouracil, capecitabine), UDP glucuronosylstransferase (UGT1A1) for irinotecan and thiopurine S-methyltransferase (TPMT) for thiopurine drugs. Depending on the level of evidence, the French National Network of Pharmacogenetics (RNPGx) has issued three levels of recommendations for these pharmacogenetic tests: essential, advisable, and potentially useful. Other applications, for which the level of evidence is still discussed, will be evoked in the final section of this review.
个体化治疗在肿瘤学中具有特殊重要性,因为用于化疗的药物治疗指数非常窄。药物遗传学可能对优化癌症治疗的临床常规有很大贡献,以在保持疗效的同时限制毒性作用。本综述介绍了药物遗传学检测在一些关键应用中的作用:用于氟嘧啶(5-氟尿嘧啶、卡培他滨)的二氢嘧啶脱氢酶(DPYD)基因分型、用于伊立替康的尿苷二磷酸葡萄糖醛酸转移酶(UGT1A1)以及用于硫嘌呤类药物的硫嘌呤甲基转移酶(TPMT)。根据证据水平,法国国家药物遗传学网络(RNPGx)针对这些药物遗传学检测发布了三个推荐级别:必要、建议和可能有用。其他证据水平仍在讨论的应用将在本综述的最后部分提及。