HOLLYWOOD, FLA. — Low-molecular-weight heparin should be the drug of choice for the initial treatment of deep vein thrombosis in cancer patients, according to new management recommendations developed by the National Comprehensive Cancer Network.
“In cancer patients, low-molecular-weight heparin results in lower risk of recurrence of venous thrombosis and a reduced risk of major bleeding, compared with warfarin,” Mohammad Jahanzeb, M.D., reported at the annual conference of the 19-center NCCN.
Many studies have confirmed a strong association between cancer and venous thromboembolism (VTE), said Dr. Jahanzeb, chair of the NCCN panel on the management of deep vein thrombosis in cancer. Patients with cancer have a higher risk of progressive and recurrent VTE, as well as an increased risk of bleeding. The association between cancer and VTE is thought to be both a consequence of tumor growth and host inflammatory responses as well as an indirect result of cancer treatment, venous stasis, and direct vessel trauma.
Traditionally, long-term anticoagulation therapy with warfarin has been the standard treatment for cancer patients with VTE, but its use has many disadvantages in this population. Cancer patients being treated for VTE experience a higher failure rate of warfarin, compared with patients who do not have cancer, he said. Warfarin can exacerbate cancer-related bleeding problems, can be difficult to manage in the presence of cancer-related comorbidities and concurrent medications, and is associated with an increased risk of adverse events in cancer patients.
In contrast, results of a metaanalysis of studies conducted during the past 7 years suggest that low-molecular-weight heparins are associated with a lower risk of adverse events, compared with warfarin in patients with cancer, said Dr. Jahanzeb, chief of the division of hematology and oncology, University of Tennessee, Memphis.
The landmark CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer) compared injection of the low-molecular-weight heparin dalteparin with intravenous warfarin therapy for treating cancer patients with symptomatic, newly diagnosed deep vein thrombosis and/or pulmonary embolism. The dalteparin group had 52% fewer recurrent clots over the 6-month study period, with no significant increase in the incidence of bleeding, Dr. Jahanzeb said.
And in nine randomized controlled trials that examined 3-month mortality in cancer and noncancer patients, those who received low-molecular-weight heparin had a significantly greater survival benefit than those who did not. It has been hypothesized that the antineoplastic effects of low-molecular-weight heparins may alter the natural history of malignant disease, he noted.
Low-molecular-weight heparins also have practical advantages over warfarin. Warfarin requires frequent dose monitoring because of substantial variability between and within the same individuals (which is exaggerated in cancer patients). Low-molecular-weight heparin has more predictable anticoagulant effects and thus does not require the same degree of monitoring. Subcutaneous injections of low-molecular-weight heparin can be done in the outpatient setting, but intravenous warfarin treatment usually is done on an inpatient basis, Dr. Jahanzeb reported.
“The data consistently suggest that [low-molecular-weight heparin] is safe and effective for the treatment and secondary prevention of venous thrombosis in cancer patients,” he said.
It also should be considered for prophylaxis in certain subgroups of cancer patients, such as those with extensive disease or poor vascular access.