Nonselective Beta-Blockers Linked to Improved Ovarian Cancer Survival

By Will Boggs MD

NEW YORK - Use of nonselective beta-blockers is associated with longer overall survival in women with ovarian cancer, according to results from a retrospective study.

"We were not certain whether there would be a difference between the different types of beta-blockers," Dr. Anil K. Sood, from the University of Texas MD Anderson Cancer Center, Houston, told Reuters Health by email. "Preclinical data suggested that the nonselective beta-blockers would be more effective -- and that was indeed the finding in this study."

Activation of adrenergic receptors on ovarian cells contributes to the growth and progression of ovarian cancer, but studies that have investigated the impact of beta-blockers on survival in women with ovarian cancer have yielded conflicting results.

Dr. Sood's team examined the impact of selective versus nonselective beta-blockers on overall survival in a retrospective study of 1425 women with newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively referred to as epithelial ovarian cancer, EOC).

Beta-blocker use in general was associated with improved disease-specific and overall survival, according to the August 24 online report in Cancer.

In subgroup analyses, only women who also had hypertension experienced improved survival associated with selective beta-blocker use.

In contrast, nonselective beta-blocker use was associated with improved disease-specific and overall survival regardless of the presence of hypertension.

Normotensive nonselective beta-blocker users had the longest median overall survival (112 months), and the entire group of nonselective beta-blocker users had a longer median overall survival (90 months) than either users of selective beta-blockers or nonusers with elevated blood pressure.

"The caution is that this is a retrospective study and additional studies are needed for validation," Dr. Sood concluded.

"There are currently two clinical trials that are evaluating the combination of chemotherapy and variable doses of propranolol on cancer biology, as well as the effect of nonselective beta-blockers on stress modulators in patients newly diagnosed with EOC," the researchers noted. "The preliminary data from these feasibility trials will help us to design adequately powered, prospective, randomized clinical trials to determine whether nonselective beta-blockers can improve outcomes for patients with EOC."

"There is no doubt that adrenergic stimulation negatively modulates the ovarian tumor microenvironment and promotes proliferative signaling and malignant progression," Dr. Kristen P. Bunch and Dr. Christina M. Annunziata, from the National Cancer Institute, Bethesda, Maryland, wrote in a related editorial. "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 effective therapies," they concluded. "The results reported in the study are certainly intriguing and provide further evidence in support of intensifying research efforts into the application of beta-blockers as an anticancer strategy."

Dr. Florian Heitz, from Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung, Essen, Germany, recently reported on the lack of impact of beta-blockers on survival in recurrent ovarian cancer. He told Reuters Health by email, "Nonselective beta-blockers should be tested in clinical trials."

"There are hints that stress by itself might have a prognostic impact on progression and survival of patients with ovarian cancer," Dr. Heitz said, "and this should be further investigated, that is, whether stress-reducing behavioral changes might optimize outcomes of patients with cancer."

One coauthor reported relationships with Incyte Pharmaceuticals and Egen Pharmaceuticals, now owned by Celsion. Both companies develop anti-cancer drugs.

SOURCE: https://bit.ly/1V5dN3Q and https://bit.ly/1EiZrbI

Cancer 2015.

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