Increased incidence of grade 3 or higher fluorouracil adverse events were linked with dihydropyrimidine dehydrogenase gene DPYD variants in patients with resected stage 3 colon cancer treated with adjuvant fluorouracil-based combination chemotherapies, according to a study published in JAMA Oncology.1
Investigators sought to determine the prognostic significance of DYPD variants on fluorouracil-related adverse events in patients treated with the FOLFOX4 regimen (fluorouracil, leucovorin, and oxaliplatin), in a secondary analysis of the PETACC-8 randomized clinical trial.
A total of 1545 patients were genotyped on 25 DPYD variants and were randomly assigned to receive standard adjuvant FOLFOX4 alone or FOLFOX4 plus cetuximab for 6 months.
Results showed that carriers of D949V and V732I (DPYD*6) had an incidence of grade 3 or higher fluorouracil adverse events of 85.7% 60.8% patients, respectively. Researchers adjusted for multiple variables and associations were found between grade 3 or higher fluorouracil adverse events and both D949V and V732I variants (odds ratio [OR], 6.3; 95% CI, 2.0 – 27.0; P < .001; and OR 1.7; 95% CI, 1.3 – 2.4; P < .001, respectively).
RELATED: Medicare Coverage for Computed Tomography Colonography Proposed
Participants with V732I and D949V variants experienced greater grade 3 or higher overall hematologic adverse events (OR, 1.9; 95% CI, 1.4 – 2.6; and OR, 5.2; 95% CI, 2.0 – 16.0, respectively).
Participants with V732I variants experienced higher rates of grade 3 or higher neutropenia (OR, 1.8; 95% CI, 1.3 – 2.4). The association of V732I and the occurrence of grade 3 or higher hematologic events related to fluorouracil were validated in an independent cohort of 399 patients.
The authors concluded that further studies are needed to confirm and quantitate the associations.
- Boige V, Vincent M, Alexandre P, et al. DPYD genotyping to predict adverse events following treatment with flourouracil-based adjuvant chemotherapy in patients with stage III colon cancer: a secondary analysis of the PEDTACC-8 randomized clinical trial [published online ahead of print January 21, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.5392.