Capecitabine-Induced Severe Toxicity Secondary to DPD Deficiency and Successful Treatment with Low Dose 5-Fluorouracil

UMMS Affiliation

Department of Internal Medicine; Department of Medicine, Division of Hematology and Oncology; Department of Radiation Oncology

Publication Date


Document Type



Digestive System Diseases | Gastroenterology | Neoplasms | Oncology | Radiation Medicine | Radiology | Therapeutics


Colorectal cancer is the third most common cancer and second leading cause of cancer-related death in the United States [1]. Fluoropyrimidines are the back bones of systemic chemotherapy in colorectal cancer. Currently, two forms of fluoropyrimidines, an intravenous 5-fluorouracil (5-FU) and its oral prodrug capecitabine, are widely used in the western world. Nearly 1/3 of patients with colorectal malignancies experience grade 3 or greater toxicities associated with the use of fluoropyrimidines, and treatment-related mortality rate approaches 0.5 % [2].

Dihydropyrimidine dehydrogenase (DPD) is a key enzyme involved in rate limiting step during metabolism of 5-FU and capecitabine. Approximately 80 % of the administered fluoropyrimidines are metabolized by through this pathway. Less than 2 % will be metabolized by anabolic pathways to exhibit cytotoxic effects on tumor cells (Fig. 1) [3]. DPD deficiency has been associated with severe and lethal toxicities with 5-FU which have been well documented [4].


Oxaliplatin, Capecitabine, Intensity Modulate Radiation Therapy, Fluoropyrimidines, Raltitrexed

DOI of Published Version



J Gastrointest Cancer. 2017 Mar;48(1):66-69. doi: 10.1007/s12029-015-9797-x. Link to article on publisher's site

Journal/Book/Conference Title

Journal of gastrointestinal cancer

Related Resources

Link to Article in PubMed

PubMed ID