Tinzaparin did not improve survival in patients with colorectal cancer: BMJ

Canada: Extended duration of perioperative anticoagulation with tinzaparin did not impact the disease-free survival or overall survival in patients with colorectal cancer following surgery, says an article published in the British Medical Journal. 

Tinzaparin, a low molecular weight heparin, has demonstrated antimetastatic properties in preclinical models by possibly preventing tumor cell invasion of the extracellular matrix, impeding immune-mediated destruction of tumor cells in the circulation, and preventing the neovascularization of micro-metastases due to an antiangiogenic effect. 

Between October 25, 2011, and December 31, 2020, 12 hospitals in Quebec and Ontario, Canada, participated in this multicenter, open label, randomized controlled experiment. Participants 614 people (age 18) who had invasive adenocarcinoma of the colon or rectum that had been pathologically verified, showed no signs of metastatic illness, had hemoglobin concentrations below 8 g/dL, and were planned for surgical resection were eligible. When compared to in-patient postoperative thromboprophylaxis alone, extended duration thromboprophylaxis with daily subcutaneous tinzaparin at 4500 IU, starting at the decision to operate, lasts for 56 days. The main result was disease-free survival at three years, which was defined as survival without death, distant metastases, a second primary for the same cancer, a second primary for a different malignancy, or locoregional recurrence. Secondary results were five year overall survival, serious surgical bleeding problems, and venous thromboembolism. Intent-to-treat analysis was conducted on this population.

The key findings of this study were:

1. 235 (77%) of the 307 patients in the prolonged duration group and 243 (79%) of the 307 patients in the in-hospital thromboprophylaxis group experienced the main result.

2. Five patients (2%) in the prolonged period group and four patients (1%) in the in-hospital thromboprophylaxis group experienced postoperative venous thromboembolism (P=0.8).

3. One individual (1%) in the prolonged duration group and six (2%), who received in-hospital thromboprophylaxis, experienced major surgery-related bleeding in the first postoperative week (P=0.1).

4. There was no difference in overall survival at five years between the 272 (89%) extended duration patients and the 280 (91%) in-hospital thromboprophylaxis patients.

Reference: 

Auer, R. C., Ott, M., Karanicolas, P., Brackstone, M. R., Ashamalla, S., Weaver, J., Tagalakis, V., Boutros, M., Stotland, P., Marulanda, A. C., Moloo, H., Asmis, T., … Carrier, M. (2022). Efficacy and safety of extended duration to perioperative thromboprophylaxis with low molecular weight heparin on disease-free survival after surgical resection of colorectal cancer (PERIOP-01): multicentre, open label, randomised controlled trial. In BMJ (p. e071375). BMJ. https://doi.org/10.1136/bmj-2022-071375