Dalteparin low molecular weight heparin (LMWH) in ovarian cancer: a phase II randomized study.

Objective: Low molecular weight heparin reduces the risk of venous thromboembolism (VTE) and may have antineoplastic effects by interfering with angiogenesis and with tumor growth and metastasis. A multicentre phase II randomized trial was done to evaluate the antineoplastic potential of dalteparin in ovarian cancer (OC).

Materials And Methods: Women with newly-diagnosed epithelial OC were randomized to receive standard chemotherapy (CT) and one of 3 doses of dalteparin (50 IU/kg, 100 IU/kg, or 150 IU/kg) subcutaneously once daily during the first 3 of 6 cycles of 3-weekly CT. Blood was drawn on day 1 of each cycle for CA125 and, in a substudy of randomized patients, for markers of coagulation activation and angiogenesis. The primary outcome was tumor response defined by ≥ 50% reduction in serum CA125 from baseline sustained for at least 28 days. Patients were followed until the end of CT.

Results: The study was terminated early due to poor recruitment. Seventy-seven women were evaluable for the primary outcome. A 50% drop in CA125 at the end of cycle 3 was seen in 85% of the 50 IU/kg group, 92% of the 100 IU/kg group, and 85% of the 150 IU/kg group. There were no symptomatic VTE or major bleeding events while on dalteparin. Two patients experienced VTE several days after discontinuing study drug. Women on dalteparin had lower levels of D-dimer and thrombin-antithrombin, and higher levels of tissue factor pathway inhibitor, relative to baseline.

Conclusion: Dalteparin is safe and well tolerated in women receiving CT for newly-diagnosed epithelial OC. A dose-response effect was not identified. The lack of control group precluded any inference on the antineoplastic effect of dalteparin.