title: Venous thromboembolism and nonsmall cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group trials.
abstract: BACKGROUND
  Advanced nonsmall cell lung cancer (NSCLC) is associated with venous thromboembolism (VTE). However, to the authors' knowledge, the incidence of VTE in early NSCLC, predictors of VTE, and the prognostic significance of VTE in NSCLC have not been explored.
  
  
  METHODS
  Individual patient data from 3 National Cancer Institute of Canada Clinical Trials Group trials were analyzed (n = 1987 patients). Clinical Trial BR.10 was a randomized study of postoperative vinorelbine and cisplatin versus observation in patients with stage IB/II NSCLC (grading determined according to the TNM staging system). Clinical Trial BR.18 was a randomized study of paclitaxel and carboplatin with or without the metalloproteinase inhibitor BMS-275291 in patients with advanced NSCLC. BR.21 was a randomized study of erlotinib versus placebo in patients with previously treated NSCLC. The relations between VTE, treatment, concomitant medications, and patient characteristics were explored in univariate and multivariate analyses. Survival analysis was completed using Cox regression.
  
  
  RESULTS
  The incidence of VTE ranged from 0% in patients with early stage NSCLC on the observation arm of BR.10 to 7.9% in patients with advanced NSCLC who received chemotherapy (BR.18). Patients with early stage NSCLC who received chemotherapy (BR.10) and patients with previously treated NSCLC who received erlotinib or placebo (BR.21) had a VTE incidence of approximately 3%. Factors that were found to be predictive of VTE included previous VTE (BR.18; P = .001) and obesity (BR.10; P = .03). In patients with advanced NSCLC, VTE was associated with shorter survival (BR.18: hazard ratio [HR], 1.61; 95% confidence interval [95% CI], 1.26-2.07 [P = .0002]; BR.21: HR, 2.18; 95% CI, 1.57-3.04 [P < .0001]).
  
  
  CONCLUSIONS
  In patients with both early stage and advanced stage NSCLC, VTE occurred more frequently in patients who received chemotherapy (but not erlotinib or BMS-275291). In patients with advanced stage NSCLC, VTE was associated with obesity and a history of VTE. VTE was found to be prognostic in patients with advanced stage NSCLC.
authors.affiliation: Keenan Research Center, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. hicksl@smh.toronto.on.ca
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Hicks
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cheung
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.forename: Baktiar
authors.initials: B
authors.lastname: Hasan
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: Aurélie
authors.initials: A
authors.lastname: Le Maître
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D005260:Female; D005544:Forecasting; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis; D054556:Venous Thromboembolism / Q000150:complications*