title: Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.
abstract: OBJECTIVE
  Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy.
  
  
  METHODS
  A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1).
  
  
  RESULTS
  The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy.
  
  
  CONCLUSIONS
  Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.
authors.affiliation: Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy. mberretta@cro.it.
authors.forename: R
authors.initials: R
authors.lastname: Di Francia
authors.forename: L
authors.initials: L
authors.lastname: De Lucia
authors.forename: M
authors.initials: M
authors.lastname: Di Paolo
authors.forename: S
authors.initials: S
authors.lastname: Di Martino
authors.forename: L
authors.initials: L
authors.lastname: Del Pup
authors.forename: A
authors.initials: A
authors.lastname: De Monaco
authors.forename: A
authors.initials: A
authors.lastname: Lleshi
authors.forename: M
authors.initials: M
authors.lastname: Berretta
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics; D005838:Genotype; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil