23: PERIOP-01: A Randomized Controlled Trial of Extended Perioperative Tinzaparin to Improve Disease-free Survival in Patients with Resectable Colorectal Cancer
Scientific Director, Cancer Therapeutics Program Ottawa Hospital Research Institute Ottawa, ON, Canada
Disclosure: Leo Pharma Inc. (Individual(s) Involved: Self): Research Grant or Support
Participants should be aware of the following financial/non-financial relationships:
Rebecca C. Auer, MD, MSc, FRCSC, FACS: Leo Pharma Inc. (Individual(s) Involved: Self): Research Grant or Support
Introduction: Cancer patients undergoing surgical resection of their tumor are hypercoagulable beyond the period of hospitalization. Preclinical studies demonstrate that the postoperative hypercoagulable state promotes metastases, an effect that is abrogated by administration of perioperative low molecular-weight heparin (LMWH).
Methods: We conducted a randomized, open label clinical trial to determine if extended duration thromboprophylaxis using subcutaneous LMWH (tinzaparin 4,500 IU daily), beginning at decision to operate and continuing for 56 days postoperatively, compared to inpatient postoperative thromboprophylaxis only, increased the 3-year disease-free survival (DSF) in patients undergoing resection for colorectal cancer. Secondary outcomes included 5-year overall survival (OS),postoperative bleeding and venous thromboembolism (VTE).
Results: Trial recruitment was stopped prematurely after 614 of the planned 1075patients were registered, following a pre-defined interim analysis for futility. The intention-to-treat analysis included 602 patients with demographics in Table 1. The 3-year DFS was 78.9% (63/299 recurrences) in the tinzaparin group and 80.5%(59/303 recurrences) in the control group (hazard ratio (HR) 1.09; [95% CI0.91,1.31; p = 0.3]). The 5-year OS was 91.3% in the tinzaparin group and 92.4% in the control group (HR 1.08; [95% CI 0.66,1.79; p = 0.1]). The incidence of postoperative VTE was 1.7% and 1.3% in the tinzaparin and control groups respectively (HR 1.3; [95% CI 0.30,5.69; p = 0.7]. The incidence of major bleeding in the first postoperative week was 0.3% and 2% in the tinzaparin and control groups, respectively (HR 0.16; [95% CI 0.02,1.15; p = 0.07].
Conclusions: Extended duration perioperative anticoagulation with tinzaparin did not improve DFS or OS in colorectal cancer patients undergoing surgical resection. The incidences of postoperative bleeding and VTE were low. (Funded by Canadian Institute of Health Research and Leo Pharma; ClinicalTrials.gov NCT 01455831).
Learning Objectives:
Upon completion, participants will be able to describe the effect of postoperative extended duration low molecular heparin on overall and disease-specific survival in colorectal cancer surgery patients.
Upon completion, participants will be able to describe the effect of postoperative extended duration low molecular heparin on venous thromboembolism events in colorectal cancer surgery patients.
Upon completion, participants will be able to summarize the current clinical trial literature on the effect of extended duration postoperative low molecular weight heparin in patients with colorectal cancer.
