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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Patients with advanced ovarian cancer had significantly better survival if they took beta-blockers, particularly the noncardioselective agents. Overall, beta-blocker users lived about 6 months longer than did nonusers. However, difference more than doubled to a median survival of almost 8 years in the subgroup of patients treated with nonselective beta-blockers. The findings add to evidence from other types of cancer supporting a beneficial effect of beta-blockers on survival and other outcomes. The improved survival with nonselective beta-blockers suggests a potential for novel therapeutic approaches for epithelial ovarian cancer.”

Recently, studies in several types of cancer have demonstrated improved outcomes, including survival, in patients who used beta-blockers. Several lines of evidence support a biologic rationale for a beneficial effect beta-blockers in cancer. Physiologic changes associated with social isolation, depression, and stress includes increased production of the stress-related hormones norepinephrine and epinephrine, which are targeted by beta-blockers. Increased production of stress hormones has been shown to promote cancer-cell growth, progression and spread in several types of cancer, including ovarian cancer, the investigators noted. With respect to specific effects in ovarian cancer, in vitro studies have shown that epithelial ovarian cancer cells express beta-1 and beta-2 adrenergic receptors. Norepinephrine stimulation of ovarian cancer cells induces vascular endothelial growth factor, matrix metalloproteinases, and cancer-cell growth and invasion. Propranolol, a nonselective beta-blocker, has been shown to inhibit the stimulatory effects of norepinephrine on epithelial ovarian cancer cells.

The effects of beta-blockers was examined on survival in patients with epithelial ovarian cancer treated with chemotherapy. Investigators at five medical centers retrospectively identified patients (median age 61) with stage III or IV ovarian cancer and compared records of patients who had been treated with beta-blockers and those who had not. The analysis included 1,425 patients, including 269 patients whose records documented use of beta-blockers. Nonselective agents accounted for 195 (72%) of the beta-blocker users. More than 90% of beta-blocker users had hypertension, compared with 30% of the 1,158 patients who did not receive the drugs. Demographics, disease stage, and surgical outcomes did not differ significantly between beta-blocker users and nonusers.

Patients who did not use beta-blockers had a median overall survival (OS) of 3.5 years, whereas beta-blocker users had a median OS of 3.98 years (P=0.0365). Subanalyses by type of beta-blocker showed that use of cardioselective agents was associated with a median OS of 3.17 years, whereas users of nonselective agents had a median OS of 7.91 years (P<0.0001 versus nonusers). Beta-blocker users also had superior disease-specific survival (DFS), a median of 48.4 months versus 42.4 months for nonusers (P=0.02). Patients who used nonselective beta-blockers had a median DFS of 90 months versus 38.2 months for patients taking cardioselective agents (P<0.001).

The study provided “provocative information” regarding potential novel therapeutic applications of beta-blockers in the treatment of ovarian cancer. In particular, the findings pertaining to nonselective beta-blockers warrant further study. However, the investigators did not perform a multivariate analysis to identify factors that might have explained the results. There remains a significant risk of selection bias and other confounders that may have accounted for some of the survival differences observed.

Source References:

http://www.medpagetoday.com/MeetingCoverage/SGO/37838

 

http://www.ncbi.nlm.nih.gov/pubmed/22819786

 

http://www.ncbi.nlm.nih.gov/pubmed/23500609

 

http://www.ncbi.nlm.nih.gov/pubmed/18398660

 

http://www.ncbi.nlm.nih.gov/pubmed/21317458

 

http://clinicaltrials.gov/ct2/show/NCT01308944

 

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