Predictive Testing for DPD Deficiency in a Patient With Familial History of Fluoropyrimidine-associated Toxicity

Felicia Stefania Falvella; Stefania Cheli; Filippo de Braud; Emilio Clementi; Filippo Pietrantonio

Disclosures

Personalized Medicine. 2014;11(3):259-262. 

In This Article

Abstract and Introduction

Abstract

Reduced activity of DPD leads to severe toxicity in cancer patients receiving standard doses of fluoropyrimidines, particularly in the case of combination regimens. We describe a 38-year-old man with a resectable metastasis from hereditary nonpolyposis colorectal cancer, with indication of neoadjuvant chemotherapy and a family history of fluoropyrimidine-associated toxicity. We tested our patient for functional DPYD variants, before any choice of the neoadjuvant regimen, including for the c.496A>G, already described in his mother, and a deep intronic variant c.1129–5923C>G recently reported associated to severe toxicity. Our patient was found to be heterozygous for both c.469A>G and c.1129–5923C>G DPYD variants. We thus offered the most active perioperative regimen, capecitabine, oxaliplatin, irinotecan plus bevacizumab by which we reduced the dosing of capecitabine to 50%. Treatment was well tolerated, with grade 2 diarrhea as the most significant adverse event, and led to a complete pathological response after liver resection. We provide a rationale approach to improve the safety of fluoropirimidine-based therapy in a patient with family history of fluoropyrimidine-associated toxicity.

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