Heparin Works as Prophylaxis for Cancer Patients

[RandyW]

Heparin Works as Prophylaxis for Cancer Patients

By Todd Neale, Staff Writer, MedPage Today

Published: September 01, 2009

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and

Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit

for reading medical news

Action Points

* Explain to interested patients that nadroparin is not currently available in the U.S.

* Explain to patients that most physicians do not use prophylactic anticoagulation in cancer patients receiving chemotherapy in an outpatient setting.

Prophylactic nadroparin (Fraxiparine), a low-molecular-weight heparin, significantly reduced the risk of thromboembolism in cancer patients receiving outpatient chemotherapy, a randomized trial showed.

After four months of treatment, just 2% of patients with advanced cancer who received nadroparin had a symptomatic venous or arterial thromboembolic event, compared with 3.9% of those who received placebo (P=0.02), according to Giancarlo Agnelli, MD, of the University of Perugia in Italy, and colleagues.

More patients in the nadroparin group had a major bleeding event (0.7% versus 0%), but the difference did not reach statistical significance (P=0.18). The study was not powered for this endpoint.

Rates of minor bleeding were similar in the two groups (7.4% with nadroparin and 7.9% with placebo).

The results, published online in The Lancet Oncology, were originally reported at the American Society of Hematology meeting in December. (See ASH: Prophylactic Blood-Thinners Prevent Thromboembolism in Cancer Patient)

Although it is well known that cancer patients receiving chemotherapy have an increased risk of thromboembolic events, the researchers said, there has been little research on the use of prophylactic blood thinners in ambulatory patients.

To help address the issue, Agnelli and his colleagues undertook the PROTECHT (Prophylaxis of Thromboembolism During Chemotherapy) trial, which was conducted at 62 Italian centers.

The investigators randomized 1,150 adult patients receiving chemotherapy for metastatic or locally advanced lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer in a 2:1 ratio to once-daily subcutaneous nadroparin (3,800 IU anti-Xa) or placebo.

Treatment lasted for the duration of chemotherapy up to a maximum of 120 days.

The researchers tracked the occurrence of all thromboembolic events, including symptomatic deep-vein thrombosis of the lower or upper limbs, pulmonary embolism, visceral or cerebral venous thrombosis, acute myocardial infarction, ischemic stroke, acute peripheral arterial thromboembolism, and unexplained death of possible thromboembolic origin that occurred during treatment or within 10 days after it was stopped.

The rate of this composite endpoint was highest among patients with lung cancer (3.5% with nadroparin versus 8.8% with placebo, P=0.07 in a post-hoc analysis).

Rates of serious adverse events and mortality one year after randomization were similar in the two groups.

The authors said the lack of a survival advantage in the nadroparin group could be explained by the shorter duration of the current study compared with those focused on survival, the use of a lower dose than that shown to be beneficial in survival, and the more advanced disease of the study population.

They acknowledged that the study was limited by its short duration and by the heterogeneity of the cancer sites and chemotherapy regimens.

"Future studies should focus on patients at high risk for thromboembolism, such as patients with lung cancer or patients identified through the use of scores that have recently been proposed to optimize patient risk stratification," they said.

The study was funded by Italfarmaco, maker of nadroparin.

One of the study authors is the scientific director of Italfarmaco. Agnelli and the rest of the authors reported that they had no conflicts of interest.

Primary source: The Lancet Oncology

Source reference:

Agnelli G, et al "Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomized, placebo-controlled, double-blind study" Lancet Oncol 2009; DOI: 10.1016/S1470-2045(09)70232-3.