title: Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer.
abstract: OBJECTIVE
  We evaluated the efficacy of gemcitabine versus gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer (NSCLC) and a performance status (PS) of 2 and assessed if tumoral RRM1 and ERCC1 protein levels are predictive of response to therapy.
  
  
  METHODS
  A randomized phase III trial was conducted in community-based oncology practices. Tumor specimens were collected a priori and shipped to a single laboratory for blinded determination of in situ RRM1 and ERCC1 protein expression levels by an automated quantitative immunofluorescent-based technology.
  
  
  RESULTS
  One hundred seventy patients were randomly assigned. Overall median survival was 5.1 months for gemcitabine and 6.7 months for gemcitabine and carboplatin (P = .24). RRM1 (range, 5.3 to 105.6; median, 34.1) and ERCC1 (range, 5.2 to 131.3; median, 34.7) values were significantly and inversely correlated with disease response (r = -0.41; P = .001 for RRM1; r = -0.39; P = .003 for ERCC1; ie, response was better for patients with low levels of expression). A model for response prediction that included RRM1, ERCC1, and treatment arm, was highly predictive of the treatment response observed (P = .0005). We did not find statistically significant associations between survival and RRM1 or ERCC1 levels.
  
  
  CONCLUSIONS
  Single-agent chemotherapy remains the standard of care for patients with advanced NSCLC and poor PS. Quantitative analysis of RRM1 and ERCC1 protein expression in routinely collected tumor specimens in community oncology practices is predictive of response to gemcitabine and gemcitabine and carboplatin therapy. Oncologists should consider including in situ expression analysis for these proteins into their therapeutic decisions.
authors.affiliation: US Oncology, The Woodlands, TX, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Reynolds
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schell
authors.forename: Xueli
authors.initials: X
authors.lastname: Li
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: David
authors.initials: D
authors.lastname: Boulware
authors.forename: John R
authors.initials: JR
authors.lastname: Caton
authors.forename: Linda C
authors.initials: LC
authors.lastname: Demarco
authors.forename: Mark A
authors.initials: MA
authors.lastname: O'Rourke
authors.forename: Gail
authors.initials: G
authors.lastname: Shaw Wright
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Boehm
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Jane
authors.initials: J
authors.lastname: Bromund
authors.forename: Guangbin
authors.initials: G
authors.lastname: Peng
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Monberg
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012262:Ribonucleoside Diphosphate Reductase; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D016190:Carboplatin; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D000093542:Gemcitabine