title: Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) protein expression in patients with non-small-cell lung cancer (NSCLC) may be not only a prognostic marker but also predictive for COX-2 inhibition. We hypothesized that COX-2 expression is associated with shorter survival and that celecoxib, being a potent COX-2 inhibitor, increases tumor response and survival.
  
  
  METHODS
  A phase III study was performed in patients with stage IIIb/IV NSCLC who had pathologic confirmation, no prior chemotherapy, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Treatment consisted of docetaxel and carboplatin every 3 weeks for five cycles. Patients were randomly assigned to receive celecoxib 400 mg or placebo twice daily. COX-2 expression on tumor cells was detected by immunohistochemistry. Primary end point was overall survival (OS).
  
  
  RESULTS
  From July 2003 to December 2007, 561 patients were randomly assigned. Toxicity was mild, and no increase in cardiovascular events was observed. Tumor response was 38% in the celecoxib arm and 30% in the placebo arm (P = .08). Median progression-free survival was 4.5 months (95% CI, 4.0 to 4.8) for the celecoxib arm and 4.0 months (95% CI, 3.6 to 4.9) for the placebo arm (hazard ratio [HR], 0.8; 95% CI, 0.6 to 1.1; P = .25). Median OS was 8.2 months (95% CI, 7.5 to 8.8) for both treatment arms (HR, 0.9; 95% CI, 0.6 to 1.2; P = .32). COX-2 expression did not independently predict survival. Benefit from celecoxib, restricted to patients with low COX-2 expression, was not significant when adjusted for prognostic factors.
  
  
  CONCLUSIONS
  In advanced NSCLC, celecoxib does not improve survival. In this study, COX-2 expression was not a prognostic biomarker and had no predictive value when celecoxib was added to chemotherapy.
authors: Department of Pulmonary Diseases, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, the Netherlands. h.j.m.groen@long.umcg.nl
authors: Harry J M
authors: HJ
authors: Groen
authors: Hannie
authors: H
authors: Sietsma
authors: Andrew
authors: A
authors: Vincent
authors: Monique M H
authors: MM
authors: Hochstenbag
authors: John W G
authors: JW
authors: van Putten
authors: Anke
authors: A
authors: van den Berg
authors: Otilia
authors: O
authors: Dalesio
authors: Bonne
authors: B
authors: Biesma
authors: Hans J M
authors: HJ
authors: Smit
authors: Ariën
authors: A
authors: Termeer
authors: T Jeroen N
authors: TJ
authors: Hiltermann
authors: Ben E E M
authors: BE
authors: van den Borne
authors: Franz M N H
authors: FM
authors: Schramel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000032:analysis*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000008:administration & dosage; D011788:Quality of Life; D013449:Sulfonamides / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D011720:Pyrazoles; D013449:Sulfonamides; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib