Tests:

1. M. Levine reviewed the goals of the Hemostasis and Malignancy Subcommittee. The goals are to stimulate clinical trials that will address unanswered clinically important questions in thrombosis and cancer; and to facilitate basic research that will advance knowledge in the area of the pathophysiology of hemostasis and malignancy.
2. A. Falanga reviewed the topic of blood tests of hypercoagulation in cancer patients. The focus was on the ability of such tests to predict thrombotic events in cancer patients. There has been no new information since the Subcommittee’s previous meetings. There is clearly a need for further large prospective studies in which blood tests are performed.
3. A. Falanga reviewed the progress of the SOMIT Study, which is ongoing in Italy. In this study, patients who present with idiopathic venous thrombosis are randomized to an extensive search for an occult malignancy versus a minimal search. Entry to the study has been closed and over 200 patients have been recruited.
4. A. Lee presented the results of a prospective study that evaluated the SimpliRED D-dimer Test in cancer patients with deep vein thrombosis. The study demonstrated that in cancer patients compared to non-cancer patients, the specificity of the SimpliRED drops substantially and, in addition, the negative predictive value of the D-dimer test was substantially lower in cancer patients. The false negative rate was 21%. Thus, this test used in isolation does not reliably exclude deep venous thrombosis in cancer patients.

Surgical Prophylaxis:

5. A. Kakkar reviewed data showing that the risk of postoperative pulmonary embolism was higher in cancer patients than non-cancer patients. He described preliminary data on the ability of pancreatic tumor cell lines to inhibit the anticoagulant effect of heparin. He described a new trial, the Prism Study, that examines the duration of postoperative prophylaxis in cancer patients undergoing major surgery. Cancer patients undergoing a laparotomy receive initial tinzaparin and are randomized to continue with low molecular weight heparin versus placebo. They receive an end of study venogram.
6. M. Monreal discussed prophylaxis in the medical cancer patient. He reviewed the epidemiology of cancer and thrombosis in his hospital in Barcelona. The most common cancers associated with thrombosis were lung, colon, prostate, and breast. He reviewed data on the use of low dose warfarin and low molecular weight heparin in cancer patients with central vein catheters.
7. G. von Templehoff discussed the TOPIC Study (Thrombosis Prophylaxis in Oncologic Patients with Certoparin). Patients with metastatic breast cancer are randomized to low molecular weight heparin or no treatment. The duration of therapy is 180 days.
8. G. Agnelli presented the results on the use of dermatan sulphate in patients undergoing cancer surgery. In this multicenter Italian study, 842 patients undergoing abdominal, thoracic, gynecologic, or urologic cancer surgery were randomized to dermatan sulphate intramuscularly starting two days preoperatively versus unfractionated heparin 5,000 units three times per day. A venogram was performed on day 7. The rate of DVT/PE in the dermatan sulphate group was 15% versus 22% in the heparin group (P=0.003). The rate of proximal DVT/PE was 1.1% versus 3.5%, respectively (P=0.08). There was no difference in the rates of bleeding and mortality. Dr. Agnelli also outlined the design of a study in cancer patients with central vein catheters. They are randomized to lovenox or placebo.
9. M. Levine also described: i) the design of a trial of fragmin versus placebo in patients with pancreatic cancer–the primary outcome is mortality, ii) the design of a trial of fragmin prophylaxis in patients with glioblastoma which is being conducted by ECOG–the primary outcome is prevention of VTE, and iii) a trial of fragmin versus placebo in cancer patients with indwelling central vein catheters–the primary outcome is prevention of VTE.
10. During the discussion period on prophylaxis there were questions and discussion concerning the use of placebo controls in studies evaluating antithrombotics in patients with central vein catheters. Given that the standard of care in most centers is no prophylaxis, the general consensus was that it is reasonable and ethical to use a no-treatment control. The use of warfarin in a three-arm trial would substantially increase the sample size.

Treatment of Venous Thromboembolism:

11. M. Levine reviewed the issues related to home treatment with low molecular weight heparin in cancer patients and the duration of anticoagulant therapy for secondary prevention in cancer patients with venous thromboembolism.
12. P. Richardson discussed veno-occlusive disease of the liver in patients undergoing transplantation. This is a clinical syndrome that involves cell injury, inflammation, thrombosis, fibrosis, and necrosis. He discussed potential therapies that might modulate these pathways. One such therapy with promise is defibrotide.
13. L. Zacharski reviewed the data on the antineoplastic effect of antithrombotics. There is no new data since the Subcommittee’s last meeting.
14. A. Kakkar updated the group on the FAMOS trial in which patients with advanced cancer are randomized to placebo or fragmin low molecular weight heparin. Recruitment should go on for one more year.
15. M. Levine updated the group on the CLOT study in which patients with acute symptomatic venous thromboemoblism receive initial fragmin and then are randomized to continue low molecular weight heparin or receive oral anticoagulant therapy. The duration of treatment is six months.
16. S. Sonenberg described the design of the MALT trial. Cancer patients are randomized to six weeks of low molecular weight or placebo.

Basic Science:

17. P. Nawroth discussed the contribution of the coagulation and fibrinolytic systems to tumor angiogenesis. In particular, he discussed the effect of tissue factor and vascular endothelial growth factor (VEGF) on angiogenesis and wound healing.
18. F. Rickles discussed translational research and the potential of molecular targets of therapy, e.g., inhibition of tissue factor which suppresses tumor growth.