Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer.

Oncotarget 2017 Feb 21

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5-fluorouracil (5-FU) based chemotherapy is the most common first line regimen used in gastric and gastroesophageal junction cancer, but development of severe toxicity is a main concern in the treatment. The present study is aimed to evaluate a novel pre-treatment assay, known as the 5-FU degradation rate (5-FUDR), as a predictive factor for 5-FU toxicity. Pre-treatment 5-FUDR and gene polymorphisms related to 5-FU metabolism (DPYDIVS14+1G>A, MTHFRA1298T or C677T, TMYS TSER) were characterized in gastro-esophageal cancer patients. Association with toxicities was retrospectively evaluated, using multivariate logistic regression analysis. 107 gastro-esophageal cancer patients were retrospectively analyzed. No relation between gene polymorphisms and toxicity were detected, while low (< 5th centile) and high (> 95th centile) 5-FUDRs were associated with development of grade 3-4 toxicity (OR 11.14, 95% CI 1.09-113.77 and OR 9.63, 95% CI 1.70-54.55, p = 0.002). Compared to currently used genetic tests, the pre-treatment 5-FUDR seems useful in identifying patients at risk of developing toxicity.

Citation

Marina Borro, Andrea Botticelli, Federica Mazzuca, Elisa Concetta Onesti, Giovanna Gentile, Adriana Romiti, Bruna Cerbelli, Eva Mazzotti, Luca Marchetti, Luana Lionetto, Maurizio Simmaco, Paolo Marchetti. Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer. Oncotarget. 2017 Feb 21;8(8):14050-14057