AMSTERDAM – Cancer patients who start dalteparin to prevent a recurrence of venous thromboembolism can continue on the drug for as long as a year without an increase in bleeding risk and with stable control against another venous thromboembolism.
But the high underlying mortality risk from cancer that many of these patients face makes it hard to judge which patients will benefit from continued prophylaxis with the low-molecular-weight heparin, Dr. Ajay K. Kakkar said at the congress of the International Society on Thrombosis and Haemostasis.
A third of the patients enrolled in the trial died before the yearlong study ended, and the vast majority of the deaths were due to cancer.
"One of the most important competing risks besides thrombosis that these cancer patients face is the risk of dying from their underlying malignancy. That’s an important determinant in trying to understand whether we should continue anticoagulant treatment," said Dr. Kakkar, a professor of surgery at University College London. "It requires clinical judgment to balance the risk of recurrent venous thromboembolism against the risk of bleeding [as an adverse effect of antithrombotic treatment] in patients with deteriorating health because of their progressive cancer," he said.
About 10 years ago, a 6-month course of treatment with a low-molecular-weight heparin became standard for cancer patients with a venous thromboembolism (VTE). Results from the CLOT (Randomized Comparison of Low Molecular Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer) trial showed that dalteparin (Fragmin) was more effective than warfarin or another oral anticoagulant for preventing recurrent VTE without increasing the risk of bleeding during 6 months of treatment (New Engl. J. Med. 2003;349:146-53).
To examine the impact of dalteparin treatment during months 7-12 following VTE, Dr. Kakkar and his associates conducted an open-label, phase IV study in 334 cancer patients who had a VTE. Trial participants received dalteparin for up to 12 months at 50 centers in the United States, Europe, and Canada. The patients averaged 64 years old, half were women, 92% had a solid tumor, and almost two-thirds had metastatic disease. The most common tumor type was lung cancer, followed by colorectal cancer, and breast and pancreatic cancer. Patients began the regimen by receiving 200 IU/kg dalteparin subcutaneously daily for the first 30 days, and then they received a reduced dosage of 150 IU/kg daily for the balance of their treatment.
The study’s primary endpoint was the rate of major bleeds during months 7-12 compared with months 2-6. Major bleeding occurred in 4.6% of the patients during months 2-6, and in 4.2% of the patients who received treatment during months 7-12. The highest rate of bleeding occurred during the first month of treatment, a 3.6% rate during the first 30 days on dalteparin, the time when the dosage was at its highest.
The incidence of all bleeding events was 13.2% during the first month on treatment, 17.3% during months 2-6, and 14.8% during months 7-12.
The incidence of new or recurrent VTEs was 5.7% during the first month on treatment, 3.4% during months 2-6, and 4.1% during months 7-12. The results suggest that dalteparin continued to suppress thrombosis during extended treatment. The overall VTE rate during the first 6 months was about 9%, which matched the 9% VTE rate on 6 months of dalteparin treatment reported in the CLOT study results in 2003. A logistic regression analysis failed to identify any patient factors that were significantly linked to the development of a new or recurrent VTE.
The study was sponsored by Eisai, the company that markets dalteparin (Fragmin). Dr. Kakkar said that he has been a consultant to and has received honoraria from Eisai as well as from several other drug companies.
On Twitter @mitchelzoler