title: Phase II study of pharmacogenetic-tailored therapy in elderly colorectal cancer patients.
abstract: BACKGROUND
  Retrospective analyses suggested that a pharmacogenetic approach may allow a tailored selection of chemotherapy for metastatic colorectal cancer.
  
  
  OBJECTIVE
  We conducted a phase II study of pharmacogenetic-selected first-line chemotherapy in elderly patients with advanced colorectal cancer, with the aim to improve efficacy and to reduce toxicity in this group of patients.
  
  
  METHODS
  24 patients were enrolled in this study. Chemotherapy regimen was prospectively assigned based on TS, DPD, ERCC-1 and UGT1A1 genotyping results. Twelve patients (50%) were treated with modified FOLFIRI, 11 patients (46%) with modified FOLFOX6 and 1 (4%) with De Gramont regimen.
  
  
  RESULTS
  A partial remission was obtained in 4 cases (17%), stable disease in 8 cases (33%) and progressive disease in 12 cases (50%). Grade 3-4 neutropenia was observed in 7 patients (29%) and diarrhoea in 3 cases (12%). The trial was then interrupted according to study design requiring 13 partial remissions out of the first 24 patients enrolled as the necessary response rate level in order to continue.
  
  
  CONCLUSIONS
  Prospective selection of chemotherapy based on TS, DPD, ERCC-1 and UGT1A1 expression in elderly advanced colorectal cancer patients failed to confirm previous results. A more accurate validation of retrospective findings is warranted before these molecular markers can be used for treatment selection in the clinical practice.
authors: Clinica di Oncologia, AO Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy.
authors: Mario
authors: M
authors: Scartozzi
authors: Cristian
authors: C
authors: Loretelli
authors: Rossana
authors: R
authors: Berardi
authors: Chiara
authors: C
authors: Pierantoni
authors: Rosa Rita
authors: RR
authors: Silva
authors: Davide
authors: D
authors: Mari
authors: Riccardo
authors: R
authors: Giampieri
authors: Luca
authors: L
authors: Faloppi
authors: Mirco
authors: M
authors: Pistelli
authors: Elena
authors: E
authors: Maccaroni
authors: Alessandro
authors: A
authors: Bittoni
authors: Michela
authors: M
authors: Del Prete
authors: Eva
authors: E
authors: Galizia
authors: Stefano
authors: S
authors: Cascinu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D013940:Thymidylate Synthase / Q000235:genetics; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D004268:DNA-Binding Proteins; D042943:Dihydrouracil Dehydrogenase (NADP); D004720:Endonucleases; D014453:Glucuronosyltransferase; D013940:Thymidylate Synthase; D000099148:UGT1A1 Enzyme; C071447:ERCC1 protein, human