title: Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer.
abstract: 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.
authors.affiliation: Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), "Sapienza" University of Rome, Rome, Italy.|Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Borro
authors.affiliation: Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Botticelli
authors.affiliation: Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mazzuca
authors.affiliation: Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Elisa Concetta
authors.initials: EC
authors.lastname: Onesti
authors.affiliation: Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), "Sapienza" University of Rome, Rome, Italy.|Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gentile
authors.affiliation: Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Romiti
authors.affiliation: Department of Radiological Oncological and Pathological Sciences, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Cerbelli
authors.affiliation: Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Mazzotti
authors.affiliation: Department of Clinical Oncology, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Marchetti
authors.affiliation: Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lionetto
authors.affiliation: Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), "Sapienza" University of Rome, Rome, Italy.|Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.affiliation: Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy.|Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil
keywords: 5-FU degradation rate; 5-FU toxicity; DPYD; gastro-esophageal cancer; phenotypic test