September 9, 2015
First-Generation Beta Blockers Extend Life in Ovarian Cancer Patients Despite Complicating Factors

Houston—A generic heart medication in use for more than 50 years is being touted as a potential life-extender for women with epithelial ovarian cancer (EOC) and may hold promise for other cancer types and treatment regimens.

That’s according to a study published recently in the journal CANCER, which found that EOC patients taking beta-blockers, especially the first-generation nonselective type, had greater survival rates. Researches from The University of Texas MD Anderson Cancer Center suggest the drugs are beneficial because they block the effects of stress pathways involved in tumor growth and cancer spread.

Beta blockers generally are used to treat hypertension and other heart-related conditions, although some patients take them to help manage the physical manifestations of anxiety.

For the study, investigators performed a multi-institutional retrospective analysis of the medical records of 1,425 women with ovarian cancer treated between 2000 and 2010, comparing 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).

Results indicate that:

• For patients receiving any beta-blocker, the median overall survival was 47.8 months versus 42 months for nonusers.
• Median overall survival based on beta-blocker receptor selectivity was 94.9 months for those receiving NSBBs versus 38 months for those receiving SBBs.
• Even among patients with hypertension, a longer median overall survival was observed among users of NSBBs compared with nonusers (90 months vs. 38.2 months).

“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,” explained principal investigator Anil Sood, MD, in an MD Anderson press release. “Our research has shown that the same stress mechanisms impact ovarian cancer progression, so these drugs could play a new role in cancer treatment.”

Interestingly, Sood said that beta-blocker users in the study presented at a higher stage of disease, had an increased average BMI and were more likely to be hypertensive. While all of those factors usually are associated with decreased survival, patient taking beta-blockers had either equivalent or improved overall survival.

In further examination, the researchers determined that NSBB users had improved overall survival regardless of the presence of those types of comorbidities, although that was not true for patients who took SBBs.

Study authors suggest that the results underscore the importance of adrenergic receptor-beta-2 (ADRB2), a signaling pathway important to ovarian carcinogenesis and targeted by NSBBs versus the ADRB1 pathway targeted by SBBs.

“Some of the prior studies have had conflicting data regarding the use of beta blockers and cancer patient outcomes. This may, in part, be since the type of beta blocker medication was not considered,” Sood added. “To our knowledge, the current study is the first to examine the relationships with patient outcomes based on specific types of beta blockers.”

In an accompanying editorial, Kristen Bunch, DO, of the Walter Reed National Military Medical Center, and Christina Annunziata, MD, PhD, of the National Cancer Institute, note that, despite the small number of patients who were taking nonselective beta blockers among the participants, the review uncovered a notable survival advantage that deserves further analysis.

“This study lays the groundwork for insightful investigation into repurposing cardiovascular medications to cancer therapeutics,” Bunch and Annunziata write, while cautioning that beta blockers can cause significant side effects that could prevent their widespread use in patients with cancer. They question whether stress reduction programs could work as well.

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