The application of fluoropyrimidine-based chemotherapy in colorectal cancer treatment is known to pose significant toxicity risks, which can be mitigated by tailoring treatment according to DPYD gene variants. This study evaluates the impact of DPYD genotype-guided dosing on treatment-related toxicities and patient outcomes.

A retrospective analysis was conducted on CRC patients treated with fluoropyrimidines in adjuvant setting at The Wellbeing Services County of Ostrobothnia. Patients were divided into two cohorts based on the implementation of routine DPYD genotyping: pregenotyping (2016-2018) (n = 80) and postgenotyping (2020-2022) (n = 69). The incidence of side effects, treatment discontinuation, hospitalization, and 90-day mortality were compared between groups.

The study revealed a reduction in 90-day mortality rates among patients who underwent DPYD genotyping before treatment. Patients with pathogenic DPYD variants received ≥50% reduced doses initially, leading to no severe toxicities (grade ≥3). Class 3 variants showed similar side effect profiles and hospitalization rates as untested patients but had a lower rate of treatment discontinuation.

Upfront DPYD genotyping appears to improve patient safety in CRC patients treated with adjuvant fluoropyrimidines, leading to personalized dosing that reduces severe toxicities and early mortality. These findings underscore the importance of integrating pharmacogenetic testing in clinical oncology to optimize treatment regimens and enhance patient care.