NEW YORK — Cancer patients with certain tumor types face a high risk for recurrent venous thromboembolism, and may benefit from an extended course of intensive prophylactic treatment with a low-molecular-weight heparin.
Patients with cancer of the pancreas, gastroesophageal tract, lung, or advanced metastatic disease (especially with an unknown primary cancer) were most likely to have recurrent venous thromboembolism (VTE) despite low-intensity anticoagulant therapy with a low-molecular-weight heparin (LMWH), according to a major study in 2003, Dr. Agnes Y.Y. Lee said at a symposium on cardiovascular disease in cancer patients sponsored by the University of Texas M.D. Anderson Cancer Center, among others.
Because of this experience, Dr. Lee usually treats patients with these cancers and a recent history of VTE with a high-dose regimen of dalteparin for at least 6 months. After daily treatment with 200 IU/kg dalteparin, patients are reevaluated to assess their need to continue on this regimen, switch to a lower dalteparin dose, switch to warfarin, or stop prophylactic treatment, said Dr. Lee, a physician specializing in VTE at McMaster University, Hamilton, Ont. She stressed that using a high-dose LMWH for this long in these patients was not based on findings from a prespecified analysis in the 2003 study. Dr. Lee has received research support from Pfizer Inc., which markets dalteparin (Fragmin).
Dr. Lee ran the study that led to this practice and that proved the superiority of dalteparin over warfarin for preventing recurrent VTE in cancer patients (N. Engl. J. Med. 2003;349:146–53). Patients randomized to dalteparin received the intensive regimen (200 IU/kg daily) for the first 30 days, but then were switched to a lower dosage, about 150 IU/kg per day, to reduce their risk of bleeding complications. The results suggested this dosage reduction led to a small but discernible uptick in the overall incidence of recurrent VTE episodes. “Breakthrough” VTEs, despite ongoing dalteparin treatment at the reduced dosage, were particularly a problem in patients with the higher-risk cancer types.
Prophylaxis with an LMWH for cancer patients with a history of VTE has since been endorsed in guidelines issued by the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American College of Chest Physicians, Dr. Lee said at the meeting, sponsored by the American College of Cardiology and the Society for Geriatric Cardiology. VTE is a common problem in cancer patients, with an incidence of 1%-30% in patients not on prophylaxis, depending on their tumor type.
Results from several studies also have hinted that treatment with an LMWH might have a direct anticancer effect. One suggestion of this effect appeared in a post hoc analysis of data that they had collected in their 2003 study by Dr. Lee and her associates. The analysis showed a statistically significant 50% drop in mortality in patients without metastatic disease treated with dalteparin versus warfarin (J. Clin. Oncol. 2005;23:2123–9). Similar links between improved survival and treatment with an LMWH have been seen in other studies, Dr. Lee said at the symposium. The reduction in deaths is not explained by a reduction in VTE alone because the mortality effect continues when the LMWH is stopped. More studies are needed, Dr. Lee said.