Is capecitabine safe in patients with gastrointestinal cancer and dihydropyrimidine dehydrogenase deficiency?

Clinical Colorectal Cancer
M Wasif Saif, Robert Diasio

Abstract

Patients with cancer with dihydropyrimidine dehydrogenase (DPD) deficiency are at significant risk for severe 5-fluorouracil (5-FU) toxicity, including the risk of death. Data regarding the toxicity of capecitabine, an oral fluoropyrimidine, in patients with DPD deficiency are scarce. From 2004 to 2005, 2 patients with gastrointestinal (GI) malignancies (of the pancreas and liver) experienced severe to even life-threatening toxicities during capecitabine therapy, which resulted in death for 1 patient. A DPD enzyme assay was performed as previously defined in our laboratory. Both patients were DPD deficient upon evaluation for toxicity. Capecitabine can lead to severe and sometimes life-threatening toxicities akin to toxicities caused by 5-FU in patients with DPD deficiency. In cases of unexpected severe toxicity during capecitabine treatment, DPD deficiency should be considered. We suggest that capecitabine should not be used in patients with DPD deficiency. Screening should be considered in view of the widespread use of capecitabine and 5-FU, the severe toxicity that can develop in patients with low DPD activity, and the prevalence of the mutation.

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Citations

Jan 1, 2009·OncoTargets and Therapy·Muhammad Wasif Saif
Jul 11, 2013·Pharmacogenomics·Jai N PatelHoward L McLeod
Dec 23, 2010·Expert Opinion on Drug Safety·Muhammad Wasif Saif
Sep 12, 2013·Cutaneous and Ocular Toxicology·Saher IlyasMuhammad Wasif Saif
Nov 6, 2010·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Alvaro Arjona-SánchezFrancisco J Padillo
Oct 10, 2006·Clinical Colorectal Cancer·Muhammad Wasif SaifRobert Diasio
Jul 4, 2006·Trends in Pharmacological Sciences·Michael L MaitlandMark J Ratain
Nov 16, 2007·Trends in Pharmacological Sciences·Cédric Mercier, Joseph Ciccolini
Sep 16, 2016·Chemical Research in Toxicology·Yan LouSu Zeng
Jul 14, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yoon-Koo KangTae Won Kim
Nov 18, 2017·Medicine·Yiyan JiangXiaolei Yang
Dec 14, 2006·Cancer Chemotherapy and Pharmacology·M W SaifRobert B Diasio
Mar 16, 2019·Anti-cancer Drugs·Muhammad W Saif
Apr 18, 2008·Anti-cancer Drugs·Muhammad Wasif SaifKostas N Syrigos
Jun 1, 2021·Curēus·Artsiom KlimkoElena M Ionescu

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