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Nonselective beta-blockers may improve survival for patients with epithelial ovarian cancer
The use of nonselective beta blockers appeared to improve survival among patients with epithelial ovarian cancer, according to results of a multicenter review.
“There has been growing interest in the role of stress hormones on cancer growth and metastasis,” Anil K. Sood, MD, professor in the department of gynecologic oncology and reproductive medicine and director of ovarian cancer research at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “We and others have previously demonstrated that beta-adrenergic receptors play an important role in mediating such effects. Drugs that block these receptors are called beta-blockers and have been used for a variety of conditions such as heart disease and high blood pressure.”
Sood and colleagues sought to examine the survival impact of selective vs. nonselective adrenergic receptor beta blockade.
“Some studies have previously shown that beta-blockers may be beneficial for cancer patients, but the subtypes of these drugs had not been examined in detail,” Sood said. “In the current study, we examined the outcome of ovarian cancer patients based on whether they were taking beta-1 adrenergic receptor-selective agents (SBBs), or nonselective beta blockers (NSBBs) or no such drugs.”
The researchers conducted a chart review to identify 1,425 women (median age, 63 years; range, 21-93 years) with epithelial ovarian cancer (EOC) who were diagnosed and treated at one of four institutions between 2000 and 2010.
Overall, 269 patients (18.9%) used beta-blockers. Of these patients, 71.7% used SBBs and 28.3% used NSBBs. Hypertension was the most common reason for beta-blocker use, followed by arrhythmia and post-myocardial infarction management. Women who received beta-blockers were older, had higher BMIs, and were more likely to have hypertension.
The median OS was 47.8 months among patients using any beta-blocker compared with 42 months for non-users (P = .04).
Data stratified by beta-blocker receptor selectivity indicated women who used NSBBs had a median OS of 94.9 months compared with a 38-month OS among women who used SBBs (P < .001).
Hypertension appeared associated with worse OS in the overall study population (40.1 months vs. 47.4 months; P ˂ .001). However, NSBBs significantly improved OS compared with nonuse even among women with hypertension (90 months vs. 34.2 months; P < .001). Women with hypertension who received SBBs also had longer OS than nonusers, although to a lesser degree (38.2 months vs. 34.2 months; P = .007).
“We found that the greatest benefit was for those taking the NSBBs compared to the other two groups,” Sood said. “These findings are consistent with a growing body of research showing that beta-2 and likely beta-3 adrenergic receptors play important roles in cancer growth and spread. The current study was a retrospective analysis and additional prospective studies will be important in defining the role of these drugs for cancer patients.”
These findings support additional research in this area, Kristen P. Bunch, MD, and Christina M. Annunziata, MD, PhD, both of the Women’s Malignancies Branch of the Center for Cancer Research at the NCI, wrote in an accompanying editorial.
“Stressful experiences such as a cancer diagnosis can lead to chronic neurosensory signaling and adrenergic pathway activation,” Bunch and Annunziata wrote. “There is no doubt that adrenergic stimulation negatively modulates the ovarian tumor microenvironment and promotes proliferative signaling and malignant progression. This makes beta-adrenergic antagonists a rational therapeutic approach. Gaining a better understanding of the scope of stress hormone modulation on tumorigenesis will be essential for developing therapies. The results reported in [this study] are certainly intriguing and provide further evidence in support of intensifying research efforts into the application of beta-blockers as an anticancer strategy.”– by Anthony SanFilippo
For more information:
Anil K. Sood, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston TX 77030; email: asood@mdanderson.org.
Disclosure: Sood reports no relevant financial disclosures. One researcher reports a consultant/advisory role with Incyte Pharmaceuticals and research funding from Egen Pharmaceuticals. Bunch and Annunziata report employment roles with the federal government.