Dalteparin Low Molecular Weight Heparin (LMWH) in ovarian cancer: A phase II randomized study

Abstract

ObjectiveLow 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 MethodsWomen with newly-diagnosed epithelial OC were randomized to receive standard chemotherapy (CT) and one of 3 doses of dalteparin (50IU/kg, 100IU/kg, or 150IU/kg) subcutaneously once daily during the first 3 of 6cycles 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 28days. Patients were followed until the end of CT. ResultsThe 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 50IU/kg group, 92% of the100 IU/kg group, and 85% of the 150IU/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. ConclusionDalteparin 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.