Clinical Research Papers:

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

Marina Borro, Andrea Botticelli _, Federica Mazzuca, Elisa Concetta Onesti, Giovanna Gentile, Adriana Romiti, Bruna Cerbelli, Eva Mazzotti, Luca Marchetti, Luana Lionetto, Maurizio Simmaco and Paolo Marchetti

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Oncotarget. 2017; 8:14050-14057. https://doi.org/10.18632/oncotarget.12571

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Marina Borro1,2, Andrea Botticelli3, Federica Mazzuca3, Elisa Concetta Onesti3, Giovanna Gentile1,2, Adriana Romiti3, Bruna Cerbelli4, Eva Mazzotti3, Luca Marchetti5, Luana Lionetto2, Maurizio Simmaco1,2 and Paolo Marchetti2,3

1 Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), “Sapienza” University of Rome, Rome, Italy

2 Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy

3 Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, Rome, Italy

4 Department of Radiological Oncological and Pathological Sciences, “Sapienza” University of Rome, Rome, Italy

5 Department of Clinical Oncology, “Sapienza” University of Rome, Rome, Italy

Correspondence to:

Andrea Botticelli, email:

Keywords: 5-FU degradation rate, phenotypic test, 5-FU toxicity, gastro-esophageal cancer, DPYD

Received: August 16, 2016 Accepted: October 05, 2016 Published: October 11, 2016


Background: 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.

Methods: 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.

Results: 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).

Conclusions: Compared to currently used genetic tests, the pre-treatment 5-FUDR seems useful in identifying patients at risk of developing toxicity.

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