- Erika Cecchin, PharmD, PhD
CV
ABSTRACT
More than 21% of admissions to an oncology service are related to the management of adverse drug reactions. Germline genetic polymorphisms can identify patients at risk of toxicity. We recently demonstrated for the first time, that dose reductions of fluoropyrimidines (FP) and irinotecan (IRI) induced by DPYD and UGT1A1 genotyping in gastrointestinal cancer patients allowed patients to complete their course of treatment, with improved intensity of care. The development of the DPYD test in Europe is a successful example of clinical implementation of a pharmacogenetic test. Regulatory agencies now recommend pre-treatment genotyping for DPYD in Europe, and this was a key step in this process. Most oncology patients enrolled in Italy under PREPARE for FP-based prescribing received at least a second prescription managed by an oncologist with PGx guidelines available (at 18 months). This would encourage moving from a single drug-gene interaction analysis to a panel approach to increase cost-effectiveness and improve patient management. Moreover, the complexity of the genetics of DPYDs encourages the study of rare variants and the application of NGS techniques. Germline genetic variant burden determined by NGS could be a new pharmacogenetic marker to be further studied in the future.