A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing
Menée à partir d'une revue systématique de la littérature publiée jusqu'en décembre 2020 (17 études), cette méta-analyse évalue l'intérêt, du point de vue de la réduction des effets indésirables, d'un dosage thérapeutique basé sur des données pharmacogénétiques par rapport à un dosage établi en fonction de la surface corporelle chez des patients traités par fluoropyrimidine pour un cancer et présentant ou non une mutation génétique affectant la dihydropyrimidine déshydrogénase
Background : Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type).
Methods : A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life).
Results : Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27–0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24–0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93–1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66–2.44], p = 0.47).
Conclusion : PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response.
British Journal of Cancer , résumé, 2022