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Wu, Angela

University of British Columbia

A third of patients develop severe or life-threatening toxicities from fluoropyrimidines, a commonly prescribed chemotherapeutic. Fluoropyrimidine toxicity is often due to variation in the gene (DPYD) encoding dihydropyrimidine dehydrogenase (DPD). DPYD genotyping can be used to adjust doses to reduce the likelihood of fluoropyrimidine toxicity while maintaining therapeutically effective drug levels. However, DPYD testing was not routinely available in British Columbia. This study sought to implement an evidence-based pharmacogenetic test and integrate it into routine clinical practice. DPYD testing for six variants was offered for all patients starting on fluoropyrimidines at the BC Cancer Centre in Vancouver and then across British Columbia. In nine months, 186 patients were tested, and 14 were heterozygous variant carriers. Fluoropyrimidine-related toxicity was higher in DPYD variant carriers. Of 127 non-variant carriers who have completed chemotherapy, 18 (14%) experienced severe (grade ≥3, Common Terminology Criteria for Adverse Events version 5.0). In eight variant carriers, two (25%) experienced severe toxicity even at reduced doses. For one of these carriers who experienced severe thrombocytopenia within the first week, DPYD testing likely prevented lethal toxicity. DPYD variant carriers who tolerate reduced doses could not tolerate dramatic dose increases. One variant carrier developed toxicity and had to discontinue chemotherapy when the dose was escalated by 25%, leading to updated guidelines for physicians that outlined how they should escalate doses by 10% for variant carriers who have tolerated reduced doses for two cycles. DPYD testing is now routinely offered to all patients in British Columbia.

Text

2024-06-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/85180

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/