Abstract:
Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are,
however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and
palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropy rimidine dosing based on dihydropyrimidine dehydrogenase (DPYD) genetic polymorphism and
have been shown to reduce these AEs in patients of European ancestry. This study aimed to evalu ate, for the first time, the clinical applicability of these guidelines in a cohort of cancer patients on
fluoropyrimidine standard of care treatment in Zimbabwe. DNA was extracted from whole blood
and used for DPYD genotyping. Adverse events were monitored for six months using the Common
Terminology Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier of any
of the pathogenic variants (DPYD*2A, DPYD*13, rs67376798, or rs75017182). However, severe AEs
were high (36%) compared to those reported in the literature from other populations. There was a
statistically significant association between BSA (p = 0.0074) and BMI (p = 0.0001) with severe global
AEs. This study has shown the absence of the currently known actionable DPYD variants in the
Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in the guidelines might
not be feasible for all populations hence the call for modification of the current DPYD guidelines to
include minority populations for the benefit of all diverse patients.
