DYPD genotyping to predict toxicity in patients with stage III colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy in the PETACC-8 phase III trial.

3584 Background: Previous pharmacogenetic studies have shown the prognostic impact of several rare dihydropyrimidine dehydrogenase gene (DPYD) variants on 5-FU-related toxicity. 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). Methods: We genotyped 1545 patients with resected stage III CC treated in the PETACC-8 randomized phase III trial with adjuvant FOLFOX-4 alone or combined with cetuximab, and tested the individual associations between 25 DPYD variants and 5FU-related adverse events (5FUAEs). Logistic regressions were used to assess univariate and multivariable associations. Results: The incidence of grade ≥ 3 5FUAEs in D949V and V732I (DPYD*6) carriers were 18/21 (85.7%) and 121/199 (60.8%), respectively. After adjusting for multiple variables, statistically significant associations were identified between grade ≥ 3 5FU-AEs and both D949V (OR = 6...