Generic beta-blockers prolong overall survival in ovarian cancer

Researchers reported that patients with epithelial ovarian cancer (EOC) who received generic beta-blockers during chemotherapy demonstrated a benefit in overall survival. Those who were prescribed first-generation nonselective beta-blockers had the greatest improvement in survival, according the researchers, who published their study August 24, 2015 in the online issue of Cancer.

Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. Beta-blockers are well-known adrenergic agonists, yet little research has investigated their use in ovarian cancer.

“Beta-blockers treat a variety of conditions, such as heart disease, high-blood pressure, glaucoma, and migraines. They target a receptor protein in heart muscle that causes the heart to beat harder and faster when activated by stress hormones,” said principal investigator Anil Sood, MD, professor in Gynecologic Medical Oncology and Cancer Biology at The University of Texas MD Anderson Cancer Center, in Houston, TX. “Our research has shown that the same stress mechanisms impact ovarian cancer progression, so these drugs could play a new role in cancer treatment.”

The study was a retrospective analysis of the medical records of 1,425 women (median age 63) with ovarian cancer treated between 2000 and 2010 in multiple institutions. The researchers compared overall survival among patients with documented beta-blocker use during chemotherapy and those without. Among the 269 patients who received beta-blockers, 193 (71.7%) received beta-1-adrenergic receptor selective agents (SBBs) and the remaining patients received nonselective beta antagonists (NSBBs). Most women were taking beta-blockers for hypertension, but others were being treated for arrhythmia and postmyocardial infarction.

The researchers found:

• Median overall survival was 47.8 months for patients who received any beta-blocker vs 42 months for nonusers.
• Median overall survival based on beta-blocker receptor selectivity was 94.9 months for those receiving NSBBs vs 38 months for those receiving SBBs.
• Hypertension was associated with decreased overall survival compared with no hypertension across all groups. But even among patients with hypertension, users of NSBBs had a longer median overall survival compared with nonusers (90 months vs 38.2 months).

Interestingly, beta-blocker users in the study presented at a higher stage of disease, had an increased average body-mass index, and were more likely to be hypertensive—all factors associated with decreased survival. Yet, patients who received beta-blockers had either equivalent or improved overall survival, the researchers found.

“The stratification of patients by beta-blocker use and selectivity in this study makes it unique among all other studies examining the impact of these drugs on cancer,” Dr. Sood said. “It also builds on the mounting evidence that beta-blockers may become a key treatment component for many patients in the future.”

Dr. Sood noted that future trials will seek to identify patients who would benefit most from beta-blocker use and which beta-blocker is best for specific tumor type based on adrenergic receptor expression. These could eventually be used as an adjuvant therapy during surgical recovery and chemotherapy to decrease tumor growth, delays in wound healing, and metastasis.