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Medline ® Abstract for Reference 103

of 'Enterotoxicity of chemotherapeutic agents'

(13)C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal cancer patients.
Cunha-Junior GF, De Marco L, Bastos-Rodrigues L, Bolina MB, Martins FL, Pianetti GA, Cesar IC, Coelho LG
Cancer Chemother Pharmacol. 2013 Dec;72(6):1273-82. Epub 2013 Oct 8.
PURPOSE: Up to 30 % of patients undergoing 5-fluorouracil (5FU)-based chemotherapy experience severe toxicity. Dihydropyrimidine dehydrogenase (DPD) deficiency explains 36-61 % of cases. Predicting toxicity is an unmet challenge. Uracil breath test (UraBT) consists of measuring (13)CO2 in exhaled breath after ingestion of 2-(13)C-uracil to evaluate pyrimidine (and 5FU) catabolism.
METHODS: We studied 33 gastrointestinal cancer patients previously exposed to 5FU: Thirteen had grade 3-4 and 20, grade 0-1 toxicity. The following tests were used to evaluate pyrimidine catabolism: (1) sequencing of three exons of DPYD; (2) plasma dihydrouracil/uracil ratio (UH2/U); and (3) UraBT. We tested the performance of UraBT to discriminate patients who had grade 0-1 toxicity versus grade 3-4 toxicity and patients with and without proven DPD deficiency.
RESULTS: Of the thirteen patients, four grade 3-4 toxicity patients were proved to be DPD-deficient: Three had deleterious mutations (IVS14 + 1G>A in one; single nucleotide polymorphism 2846A>T in two), and one had low UH2/U ratio. Mean delta over baseline in 50 min (DOB50) significantly differed between groups. DOB50≤161.4 discriminated individuals with grade 3-4 versus grade 0-1 toxicity (sensitivity = 61.5 %; specificity = 85 %) and DPD-deficient versus non-DPD-deficient (sensitivity = 75 %; specificity = 85 %).
CONCLUSION: UraBT has moderate accuracy in discriminating individuals who manifested severe toxicity from those who had mild or no toxicity to 5FU.
Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Av. Professor Alfredo Balena, 110, Belo Horizonte, MG, 30130-100, Brazil, geraldo.onco@gmail.com.