Case Report: Severe Toxicity in an African–American Patient Receiving FOLFOX Carrying Uncommon Allelic Variants in DPYD

Abstract

Cancers of the colon are commonly treated with fluoropyrimidines, which often cause severe toxicities in patients with certain variants in DPYD. Y186C (rs115232898) and a variant in the 3′ untranslated region (rs12132152) are uncommon alleles previously observed in African–Americans. An African–American female underwent 5-fluorouracil-based therapy (400 mg/m² bolus, 1200 mg/m²/day over 46 h). The patient experienced severe pancytopenia after the first cycle. After 5-fluorouracil (5-FU) dose reduction (600 mg/m²/day), the steady-state 5-FU plasma concentration became 474 ng/ml (range 301–619 ng/ml) and increased following a subsequence dose increase (800 mg/m²/day; 1248 ng/ml). After a 1000 mg/m²/day dose resulted in myelosuppression, 5-FU was again de-escalated for the remaining cycles (600 mg/m²). The observed complications are likely a function of uncommon genetic variants that affect DPYD metabolism.

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The views expressed here are those of the authors and do not necessarily reflect the views of the National Cancer Institute, the National Institutes of Health, the Department of Health and Human Services or the USA government.

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The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Funding

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.