Researchers, including Alok Khorana, MD of Cleveland Clinic’s Department of Hematology and Medical Oncology, recently designed a multicenter randomized controlled trial to evaluate the benefit of outpatient thromboprophylaxis with dalteparin for cancer patients at high risk of developing venous thromboembolism (VTE).
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The trial, which was funded by the National Institutes of Health, was closed early because of poor accrual, but its finding of a high incidence of baseline VTE suggests that consideration should be given to early screening of high-risk patients in clinical practice prior to starting systematic therapy, Dr. Khorana says.
He is lead author of a paper on the trial presented at the 57th American Society of Hematology Annual Meeting & Exposition in December in Orlando, Fla.
Cancer patients are at higher risk of developing blood clots compared with the general population, and cancer-associated thrombosis significantly contributes to mortality in this patient population.
“In addition, treatment of blood clots is expensive and blood clots are largely preventable,” says Dr. Khorana. “But in the past, we didn’t know which patients were at higher risk, and so there was no good way to prevent it, unless we gave the treatment to every cancer patient, which would be sort of over-treating a lot of patients.”
In 2008, researchers led by Dr. Khorana came up with a risk score to predict which cancer patients are particularly at risk for developing blood clots, now referred to as the Khorana score.
Baseline screening for trial finds significant number of patients already have blood clots
In the more recent trial, high-risk patients (Khorana score ≥3) as defined by this previously validated risk score were randomized to either receive dalteparin, a low-molecular-weight heparin, or simply remain under observation before initiating a new chemotherapy regimen.
“We did ultrasounds of the legs before we randomized patients for getting a blood thinner and we found that 9 percent of patients already had a blood clot. So, those patients could not be randomized because they’d already developed the event,” says Dr. Khorana. “And what this finding suggests is that the high-risk patients are at such high risk for getting blood clots that they may already have a clot before they start on chemotherapy.”
“The goal was 200 patients and we ended with roughly 100 patients,” he says. “And so it’s underpowered to be statistically significant in its findings, but the findings are still quite interesting.”
Dalteparin does reduce blood clot risk in underpowered study
• Many of the cancer patients already had blood clots before they even started cancer treatment.
• The rates of thrombosis were very high in this population, confirming the validity of the risk score.
• Dalteparin was able to reduce the risk of getting blood clots.
• There was no increase in major bleeding with dalteparin, while there was an increase in clinically relevant bleeding, a common side effect of anticoagulants.
“I think that one of the important findings of this study is that maybe we should be screening all of the high-risk patients for blood clots before they start on treatment,” says Dr. Khorana.
There are two ongoing studies moving this research forward. Both are using an expanded risk definition with the risk cut-off at 2 and higher because there were so many clots already in the population of 3 and higher used in the current study. One study is being done in Canada through the Ottawa Regional Cancer Center. The second is a multinational, multisite study, led by Dr. Khorana, called CASSINI. It uses an oral agent, rivaroxaban.