DPYD Genotyping to Predict Adverse Events Following Treatment With Fluorouracil-Based Adjuvant Chemotherapy in Patients With Stage III Colon Cancer: A Secondary Analysis of the PETACC-8 Randomized Clinical Trial

JAMA Oncology
V BoigePierre Laurent-Puig

Abstract

Previous pharmacogenetic studies have shown the prognostic impact of several rare dihydropyrimidine dehydrogenase gene (DPYD) variants on fluorouracil-related adverse events (fluorouracil AEs). However, conflicting results highlight the need for prospective validation in large, homogeneous patient populations uniformly treated with current standard combination therapies used in colon cancer (CC). To determine the impact of DPYD variants on fluorouracil AEs in patients with stage III CC treated with a fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) regimen. Pharmacogenetic substudy of 1545 patients who participated from December 2005 to November 2009 in the European Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 randomized phase 3 clinical trial. Patients with resected stage III CC were randomized to receive standard adjuvant FOLFOX4 alone or FOLFOX4 combined with cetuximab for 6 months. Patients were genotyped on 25 DPYD variants. We tested the individual associations between each DPYD variant and grade 3 or greater fluorouracil AEs. A total of 1545 patients (57.6% male; median [range] age, 60 [19-75] years) were included in the analysis. The incidence of grade 3 or greater fluorouracil AEs in D949V and V732I (DP...Continue Reading

Citations

Jan 13, 2018·Clinical Pharmacology and Therapeutics·Shikshya ShresthaRobert B Diasio
May 6, 2019·Pharmaceutics·Theodore J WigleRichard B Kim
Oct 28, 2017·Frontiers in Pharmacology·Nurul-Syakima Ab MutalibRahman Jamal
Jun 13, 2020·Cancer Chemotherapy and Pharmacology·Xandra García-GonzálezLuis A López-Fernández
Dec 5, 2020·The Oncologist·Catherine JolivetFrancine Aubin
Nov 26, 2020·Pharmacogenomics and Personalized Medicine·Gemma BrueraUNKNOWN Oncology Network ASL1 Abruzzo
Jan 9, 2021·Therapeutic Advances in Medical Oncology·Natalie ReizinePeter H O'Donnell
Jun 3, 2021·Current Oncology·Joanna GotfritMichael Vickers
Nov 14, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·P García-AlfonsoF Abad-Santos

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