Bevacizumab, a cancer drug, may be associated with an increased risk of venous thromboembolism, according to an analysis of several randomized controlled trials released on November 19, 2008 in JAMA.
When a cancer forms, it necessarily undergoes the process of angiogenesis, whereby new blood vessels proliferate into the tumor. Bevacizumab is a cancer drug which inhibits this angiogenesis, and it has shown beneficial results in several manifestations including colorectal cancer, non-small cell lung cancer, renal cell cancer and breast cancer. There have been some concerns about the risk of venous thromboembolism, the presence of blood clots in deep veins, in conjunction with the use of this medication.
To determine the association of venous thromboembolism with the use of bevacizumab, Shobha Rani Nalluri, M.D., of Stony Brook University, Stony Brook, N.Y., and colleagues, performed a systematic meta-analysis of 15 randomized controlled trials (RCTs), ultimately incorporating data from 7,956 patients with various types of advanced solid tumors.
In patients administered the medication, the researchers found that all-grade venous thromboembolism was incident in 11.9% of subjects, while high-grade venous thromboembolism in particular, this proportion was 6.3%. In comparison with controls, the risk of venous thromboembolism development was 33% greater in medicated subjects. In the cases of both all-grade and high-grade venous thromboembolism, risk was significantly increased. Also, both high and low doses (5 and 2.5 mg/kg per week respectively) of the drug were associated with 31% increased risk.
While this relationship persisted for different levels of thromboembolism, it varied for different types of tumors. In patients with colorectal cancer, the highest incidence was found in subjects with colorectal cancer, with 19.1%. The lowest was found in subjects with renal cancer, with 3.0%. In other patients, those with non-small cell lung cancer had14.9%, and subjects with breast cancer had 7.3%.
The authors point out the significance of these findings: “The association of venous thromboembolism with new agents presents a challenge for recognition because many RCTs may not be powered to reveal a significant relationship. Our meta-analysis of 15 RCTs has overcome this limitation of individual trials and demonstrated that bevacizumab may be associated with a significantly increased risk of venous thromboembolism in patients with a variety of metastatic solid tumors. The increased risk is observed not only for all-grade venous thromboembolism, but also for clinically significant high-grade venous thromboembolism. This finding will help physicians and patients to recognize the risk of venous thromboembolism with the administration of bevacizumab,” they say.
Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients: A Meta-analysis
Shobha Rani Nalluri, MD; David Chu, MD; Roger Keresztes, MD; Xiaolei Zhu, MD, PhD; Shenhong Wu, MD, PhD
JAMA. 2008;300(19):2277-2285.
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Anna Sophia McKenney