Antitumoral effect of low molecular weight heparin in localized lung cancer. A randomized phase III controlled trial

Abstract

Background: Whether low molecular-weight heparins impact the survival of cancer patients remains controversial. We assessed the effect of tinzaparin on survival of patients with resected early-stage non-small cell lung cancer (NSCLC) Methods: Patients with completely resected stage I, II or IIIA NSCLC were randomized within 8 weeks of surgery to usual care with or without tinzaparin 100 IU/kg daily for 12 weeks. The primary outcome was overall survival (OS). All clinical outcomes were centrally and blindly adjudicated. Results: From August 2007 to June 2013, 549 patients were randomized to tinzaparin (n =269) or control (n = 280). A total of 359 (65.4%) and 190 (34.6%) patients had stage I and II-III disease, respectively, and 220 patients (40.1%) received adjuvant che-motherapy. Median follow-up was 5.7 years. There was no significant difference in OS between groups (Hazard Ratio [HR], 1.24; 95% Confidence Interval [CI], 0.92 to 1.68; P=0.17). Five-year OSwas 74.2% (95% CI, 68.9% to 79.9%) and 68.2% (95% CI, 62.5% to 74.4%) in the control and tinzaparin groups, respectively. There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94; 95% CI, 0.68 to 1.30; P = 0.70). In patients who received adjuvant chemotherapy, OS was lower in the tinzaparin group (HR, 1.78; 95%CI, 1.13 to 2.81; P = 0.013). Two patients in the tinzaparin group experienced serious bleeding during the treatment period. Conclusions: Adjuvant tinzaparin at a dose of 100 IU/kg/d for 12 weeks had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. Clinical trial identification: NCT00475098.