title: Pharmacogenetics of extraordinary responses to 5-FU/cisplatin chemotherapy in advanced gastric cancer -- report of 2 cases.
abstract: BACKGROUND
  Gastric cancer is often diagnosed in the metastatic stage, and only 10% of patients survive for as long as 2 years. Current chemotherapy regimens show significant treatment-related toxicities. It is crucial to identify the patients that will benefit most from certain chemotherapy regimens in order to avoid unnecessary side effects.
  
  
  METHODS
  2 patients with advanced gastric cancer repeatedly received 5-FU/cisplatin combination chemotherapy. Genomic DNA was extracted from tumor tissue and mononuclear blood cells. Genotype analysis of genes of metabolizing and DNA repair enzymes was carried out using a PCR-RFLP technique. Direct sequencing was used to identify mutations of the gene dihydropyrimidine dehydrogenase (DPD).
  
  
  RESULTS
  Prolonged survival of 51 and 29 months, respectively were observed in our 2 patients. Both patients were positive for genotypes of thymidylate synthase -- the target enzyme of 5-FU -- that are associated with improved drug response. DPD variants connected with increased toxicity were not observed. However, both patients also showed genotypes in cisplatin metabolizing enzymes which enhance the effect of the drug.
  
  
  CONCLUSIONS
  Genotype analysis in drug metabolizing enzymes of 5-FU and cisplatin provide a possible explanation for extraordinary therapy effects observed in 2 patients with advanced gastric cancer.
authors.affiliation: Medizinische Klinik II, Onkologie, Hämatologie und Knochenmarkstransplantation, Universitätsklinikum Hamburg-Eppendorf, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Eray
authors.initials: E
authors.lastname: Goekkurt
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.forename: Dieter Kurt
authors.initials: DK
authors.lastname: Hossfeld
authors.forename: Jan
authors.initials: J
authors.lastname: Stoehlmacher
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011379:Prognosis; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil