GU cancer

Nonselective beta-blockers improve survival in ovarian cancer


Perioperative nonselective beta-blockers (NSBBs) but not cardio-selective beta-blockers (SBBs) appear to confer a survival advantage for women with epithelial ovarian cancer (EOC).

A population-based cohort of 3,844 Australian women aged 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for a mean of 3.2 years.

The study included 17% of women supplied beta-blockers in the same month as their surgery – most (86%) were supplied a SBB ie atenolol (59%), metoprolol (39%) and bisoprolol (2%) while 10% were supplied a NSBB, usually propranolol (91%).

Published in the Journal of Clinical Oncology, the study found all-cause survival for the cohort was 3.7 years, with 5- and 10-year survival proportions of 0.41 (95% CI, 0.39 to 0.42) and 0.23 (95% CI, 0.22 to 0.25), respectively.

“Stratified by BB use at surgery, there were 2,123 all-cause deaths in non-BB users (66.5%), 404 deaths for SBB users (72.1%), and 39 deaths recorded for NSBB users (58.2%).”

“Unadjusted Kaplan-Meier curves show that women supplied SBBs at surgery tended toward having poorer all-cause and EOC survival compared with nonusers, whereas women supplied NSBBs appeared to have a survival advantage.”

It said beta-blockers did not appear to be associated with survival differences for deaths from other causes.

The study said the survival advantage for both all-cause and ovarian cancer–specific survival only became apparent 2 years after surgery, with an estimated 80% of women alive if supplied NSBBs at surgery compared with 69% of women alive if not supplied NSBBs.

“The estimated causal survival effect was greater for ovarian cancer–specific survival compared with all-cause survival, with generally lower relative hazards and a difference in the survival proportions extending to 10 years postsurgery.”

The study said benefit for ovarian cancer–specific survival with NSBBs at the time of surgery “support the hypothesis that the nonselective beta-blockade, shown in pilot clinical trials to reduce the adrenergic stress response during ovarian cancer treatment, could lead to slower recurrence through reduced metastases and tumorigenesis arising from the surgical trauma.”

“This hypothesis is being actively explored in other cancers with a phase II clinical trial of perioperative propranolol in women undergoing treatment for breast cancer showing reduced indicators of metastatic potential and similar trials in pancreatic cancer and melanoma.”

The investigators, including senior investigator Associate Professor Susan Jordan from the University of Queensland, said large clinical trials were urgently needed.

“Unfortunately, the repurposing of safe and inexpensive drugs, like propranolol, is hindered by the lack of immediate financial incentive for private industry to conduct a large randomised clinical trial, so a joint collaborative approach between governments, researchers, and funders will likely be required.”

 

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