Beta-Blockers May Prolong Survival in Women With Ovarian Cancer
In a first-of-its-kind study, researchers demonstrated a benefit in overall survival among patients with epithelial ovarian cancer receiving generic beta-blocker heart medications. Survival was shown to be greatest among those prescribed first-generation nonselective beta-blockers.
According to The University of Texas MD Anderson Cancer Center investigators, the drugs block the effects of stress pathways involved in tumor growth and spread. With further research, they may also prove beneficial in conjunction with other treatment regimens and across other cancer types. Study results were published by Watkins et al in Cancer.
Study Findings
The findings are the result of a multi-institutional retrospective analysis of the medical records of 1,425 women with ovarian cancer treated between 2000 and 2010. Researchers compared overall survival among patients with documented beta-blocker use during chemotherapy and those who did not use beta-blockers. Among the 269 patients who received beta-blockers, 193 (71.7%) received beta-1-adrenergic receptor selective agents, and the remaining patients received nonselective beta antagonists.
The research team found that for patients receiving any beta-blocker, the median overall survival was 47.8 months, vs 42 months for nonusers. Median overall survival based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers, vs 38 months for those receiving selective beta-blockers. Even among patients with hypertension, a longer median overall survival was observed among users of nonselective beta-blockers compared with nonusers (90 months vs 38.2 months).
This study builds on a large body of research by principal investigator Anil Sood, MD, Professor in Gynecologic Medical Oncology and Cancer Biology at MD Anderson. Results showed that stress hormones fuel progression of ovarian and other cancers, and that beta-blockers—among the most proven drugs in cardiovascular medicine—might be a new way to stifle that effect.
“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,” Dr. Sood said. “Our research has shown that the same stress mechanisms impact ovarian cancer progression, so these drugs could play a new role in cancer treatment.”
According to Dr. Sood, the usefulness of beta-blockers was unclear until now. “The ability to show improved survival using nonselective agents—which inhibit a specific stress pathway—is the culmination of years of research into ovarian cancer biology and pathogenesis.”
Dr. Sood added that 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 these factors were associated with decreased survival, yet those who received beta-blockers had either equivalent or improved overall survival. Further examination revealed that nonselective beta-blocker users had improved overall survival, regardless of the presence of such prognostic factors or comorbidities. This was not true for patients who took selective beta-blockers.
Next Steps
Although further study is needed, these results highlight the importance of adrenergic receptor-beta-2 (ADRB2), a signaling pathway important to ovarian carcinogenesis and targeted by nonselective beta-blockers (vs the ADRB1 pathway targeted by selective beta-blockers).
Future trials will seek to identify patients who would benefit most from beta-blocker use, and the best beta-blocker for a specific tumor type based on adrenergic receptor expression. Then they potentially could be used as an adjuvant therapy during surgical recovery and chemotherapy to decrease tumor growth, delays in wound healing, and metastasis. Beta-blockers may also reduce cancer-related psychological distress in newly diagnosed patients, according to the study authors.
There are currently two clinical trials evaluating the combination of chemotherapy and propranolol (a nonselective beta-blocker) on cancer biology and on stress modulators in patients with newly diagnosed epithelial ovarian cancer. According to Dr. Sood, the preliminary data from these feasibility trials will be used to design prospective, randomized clinical trials examining nonselective beta-blockers on patient outcomes.
“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. It also builds on the mounting evidence that beta-blockers may become a key treatment component for many patients in the future,” said Dr. Sood.
Dr. Sood is the corresponding author for the Cancer article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
