Background Twenty-five per cent of patients treated by 5-fluorouracil and 40% treated by irinotecan had serious adverse events (SAE).1. Forty per cent of 5-fluorouracil toxicities are due to a partial deficit of dihydropyrimidine dehydrogenase (DPD). Fifteen per cent of caucasians also have a uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzymatic polymorphism. When one of these deficits exists, patients require chemotherapy dosage adjustment in order to limit haematological and/or digestive toxicities. This year, new recommendations from our National Health Institute have been issued concerning the systematic prospective genotyping of DPD. Despite numerous SAE, this preventive genetic research is not systematically performed by oncologists.
Purpose This study highlights the medico-economic interest of the genetic screening for DPD and/or UGT1A1 deficits before the initiation of chemotherapy with 5-fluorouracil and/or irinotecan in order to optimise patients’ therapeutic care.
Material and methods The patients from one oncologist who received genetic screening between January 2015 and April 2018 were analysed. The following criteria were collected: diagnosis, cancer status, prospective or retrospective screenings, screening results, types of SAE, dose reductions, shifts of chemotherapy treatments, and hospitalisations for adverse reactions and their costs.
Results For 40 months, 51 patients (average age: 66.4 years old) were genotyped out of 310 treated (132 by fluorouracil, two by irinotecan and 176 by both). Twenty of them were prospective. The study discovered 31 deficits: five DPD deficits, 21 UGT1A1 deficits and five combined deficits without complete deficit. Among them, 18 (58%) reported significant toxicities to chemotherapy with 5-fluorouracil and/or irinotecan while four (13%) had been screened before the initiation of chemotherapy. Half (n=9) required a shift to the next chemotherapy. Five hospitalisations were identified following a serious adverse event induced by the chemotherapy. Four of them (costing €14,500) could probably have been avoided by prospective screening and a dosage adjustment at the initiation of treatment.
Conclusion SAE have led some oncologists to systematically screen for DPD and/or UGT1A1 deficit before the initiation of chemotherapy by 5-fluorouracil and/or irinotecan in order to prescribe individualised and optimised dosages. This personalised medicine takes all its significance from the new concept of care’s eco-conception.
References and/or acknowledgements 1. https://www.sciencedirect.com/science/article/pii/S0007455118300535
No conflict of interest.