**The Guidelines**

The reader is referred to the following rich evidence-based guidelines:

	- 1. Should hospitalized patients with cancer receive anticoagulation for VTE prophylaxis?
	- 2. Should ambulatory patients with cancer receive anticoagulation for VTE during systematic chemotherapy?

Venous Thromboembolism in Cancer Patients 99

treatment related factors. Symptoms of post-thrombotic syndrome include debilitating leg pain, swelling, and fibrosis. Severe manifestations may result in debilitating leg ulceration,

Pulmonary hypertension is a life-threatening condition associated with fatigue, chest pain, peripheral swelling, and increased mortality. Recent studies suggest that 4–5% of patients develop pulmonary hypertension within years after symptomatic PE, Pengo et al, 2004 (216).

a. The CLOT (Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer, N Engl J Med. 2003) study, which compared dalteparin with vitamin K antagonist (VKA) therapy, is the largest randomized trial of VTE treatment in patients with cancer (n = 672) (183). This study reported a 52% RRR in the incidence of recurrent

b. Three additional studies assessed the use of LMWH for extended VTE treatment in patients with cancer. The CANTHANOX (Secondary Prevention Trial of Venous Thrombosis with Enoxaparin) study compared 3 months of warfarin therapy with 3 months of enoxaparin therapy in patients with malignancy and proximal DVT or PE (218). Because of slow recruitment, the study was terminated prematurely. At 3 months, seven patients in the enoxaparin group had recurrent VTE or major bleeding (the combined primary end point) versus 15 patients in the warfarin group (P = 0.09). Most of the primary outcomes were due to major bleeding (five patients in the enoxaparin group versus 12 in the warfarin group). In the warfarin group, six of the patients died of major bleeding, and at the 6-month follow-up, 31% of patients in the enoxaparin group had died, compared with 38.7% of patients in the warfarin group (P = 0.25). The findings of this limited study suggest that warfarin may be associated with a higher risk of bleeding than LMWH when used as long-term VTE treatment in patients

c. The three-arm ONCENOX (Secondary Prevention Trial of Venous Thrombosis with Enoxaparin) study included 101 patients with cancer and VTE. Because of the small number of patients enrolled, no differences between the enoxaparin and warfarin groups were observed with regard to the incidence of recurrent VTE, major bleeding, or

d. The LITE (Long-Term Innohep Treatment Evaluation) study found tinzaparin to be more efficacious than warfarin in 200 patients with cancer (220). Tinzaparin treatment reduced the rate of recurrent VTE by ~50%; however, the difference was not statistically significant at the end of the 3-month treatment period. There were no differences in

Compared with warfarin, LMWHs generally reduce the overall risk of recurrent VTE when used for the extended treatment of VTE, a finding confirmed by a recently published Cochrane systematic review (221). Furthermore, LMWHs do not increase major bleeding

**Several studies have addressed treatment of VTE in patients with cancer:** 

VTE in favor of dalteparin during the 6-month study period.

mobility problems, and the need for long-term nursing care.

f. Pulmonary Hypertension

**9. Treatment of VTE** 

with cancer (218).

bleeding rates between the two groups.

death (219).

