Semuloparin, an ultra-low-molecular-weight heparin(Drug information on heparin), reduces by 64% the probability that a cancer patient undergoing chemotherapy will have a thromboembolic event. The results from the randomized phase III SAVE-ONCO trial, published in the New England Journal of Medicine, also show that the benefit is not accompanied by an increase in major bleeding, a potential side effect of semuloparin. The data were first reported last June at the American Society of Clinical Oncology (ASCO) annual meeting.
Venous thromboembolism (VTE) is a common complication among cancer patients undergoing treatment. Chemotherapy is an added risk for these patients in conjunction with surgery and prolonged bedridden states. Generally, VTE risk is dependent on many factors, including the site and stage of the cancer, type of chemotherapy, patient age, and coexisting conditions. VTE can affect as many as one in five cancer patients.
The current large-scale, placebo-controlled study may tip the scale and result in more widespread prophylaxis against VTE. VTE prevention is not currently standard of care for chemotherapy cancer patients because of the risk of bleeding and the difficulty of routine administration. Many cancer patients also do not want one more needle stab or drug on top of all of the medications and harsh therapeutics they are receiving. There have not been any substantial trials, prior to the SAVE-ONCO trial, that have shown a clear benefit for VTE prevention among chemotherapy patients.
In the SAVE-ONCO trial, 3,212 patients were given either subcutaneous semuloparin injections or placebo injections daily for 3 months. Patients in the trial had locally advanced or metastatic lung, colorectal, stomach, ovarian, pancreatic, or bladder cancer. These are all cancers that have been shown to be associated with a higher VTE risk.
The semuloparin patients had two-thirds fewer VTE incidents, 3.4% for the placebo group compared with 1.2% for the semuloparin group. Patients with bladder and pancreatic cancer, who are more at risk for VTE, had the greatest absolute reductions, although the benefit was similar across all tumor types.
Semuloparin is a type of heparin that works by blocking the activity of factor Xa, an enzyme important to the coagulation cascade that allows the formation of blood clots in the body. Semuloparin has a uniquely long half-life, up to 20 hours, allowing for a subcutaneous rather than IV injection.
“Patients who are not bothered much by daily injections of low-molecular-weight heparin can probably avert hospitalization for deep-vein thrombosis and pulmonary embolism and might live longer, if they accept an increased risk of bleeding and its subsequent treatment,” wrote Elie A. Akl of the State University of New York in Buffalo, and Holger J. Schünemann of McMaster University in Ontario, Canada in an editorial in the New England Journal of Medicine that accompanied the study publication. “Those truly seeking a survival benefit will need to deal with some uncertainty regarding whether the type and stage of their cancer are associated with the likely survival benefit provided by low-molecular-weight heparin.”
Whether semuloparin administration will become common practice is yet to be determined. Take-up is likely to be determined by patient risk. “The decision to start therapy with low-molecular-weight heparin in a patient with cancer must be based on a careful integration of the patient’s values and preferences with the consideration of clinical factors,” conclude Drs. Akl and Schünemann in their editorial.
Current ongoing studies should further elucidate which patients will derive the most benefit from VTE treatment; what, if any, is the survival benefit; and what effect, if any, low-molecular-weight heparin has on cancer growth and spread.
1. Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366:601-609.
2. Akl EA, Schünemann HJ. Routine heparin for patients with cancer? One answer, more questions. N Engl J Med. 2012;366:661-662.