Raffaele Di Francia
National Institute of Tumours of Naples, Italy
Title: Toxicity prevention by Pharmacogenomics panel test for the Fluoropyrimidine / Oxaliplatin-based therapy
Biography
Biography: Raffaele Di Francia
Abstract
The toxicity profile of Fluoropyrimidine/oxaliplatin (FluOx) is well documented and often this adverse reaction leads to the suspension of therapy and potentially compromises patient benefit. Primarily toxicities include severe gastrointestinal and hematologic events related to the Fluoropyrimidine administrations, and peripheral neuropathy associated to acute and cumulative doses of Oxalipaltin. Several strategies to prevent toxicity have been so far investigated with modest success. Same adverse drug response related to the FluOx treatment could be predicted through gene polymorphisms to be known involved with fluoropyrimidine and Oxaliplatin biotransformation. The authorreport reviews the late findings on the validated gene variants that are related to the outcomes of the patients receiving FluOx treatment. In order to prevent toxicity/resistance we suggest a validated genotyping panel of the most relevant pharmacogenomics (PG) markers, including Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), X-Ray Cross-Complementing group 1 (XRCC1) and Excision Repair Cross-Complementing group 2 (ERCC2 also named XPD). So far, a multitude of methods has been applied to assess the mutational status of these genes, without defining a golden standard for the daily diagnostic routine. We will also take in consideration the usefulness and the costs of the methods used to detect these genetic alterations for a relevant contribution of cost-effectiveness of FluOx treatment. It is well known that PGx tests performed before drug treatment, lower overall medical costs and provide higher quality and longer life expectancy. We believe that retrospective and prospective trials evaluating the pharmacoeconomic impact of genotyping test in Fluoropyrimidine/oxaliplatin-based-therapy will likely provide answers for policy making on the possibility to incorporate PGx testing into daily clinical practice.