title: Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer.
abstract: OBJECTIVE
  Although current treatment options for metastatic non-small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response.
  
  
  METHODS
  From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate.
  
  
  RESULTS
  Of 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02).
  
  
  CONCLUSIONS
  Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.
authors.affiliation: Hospital Carlos Haya, Malaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cobo
authors.forename: Dolores
authors.initials: D
authors.lastname: Isla
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Ana
authors.initials: A
authors.lastname: Montes
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Sanchez
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Nuria
authors.initials: N
authors.lastname: Viñolas
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lopez-Vivanco
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Muñoz
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.forename: Vicente
authors.initials: V
authors.lastname: Alberola
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
authors.forename: Manuel
authors.initials: M
authors.lastname: Domine
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Ronco
authors.forename: Kathleen
authors.initials: K
authors.lastname: Danenberg
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: David
authors.initials: D
authors.lastname: Gandara
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin