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Nonselective beta blockers may improve outcomes in ovarian cancer

Women with cardiovascular conditions (CVC) and ovarian cancer had better 2-year survival if they received a nonselective beta-blocker (NSBB) at or around the time of cancer surgery, a review of registries showed doctors.

Postoperative survival at two years was 80% in patients who received NSBBs versus 69% in those who did not receive NSBBs. The difference represented a 53% reduction in the hazard ratio for all-cause mortality. The NSBB subgroup also had better cancer-specific survival (CSS). The survival benefit was no longer evident at 8 years.

The beneficial effects on overall survival (OS) and CSS did not apply to women receiving cardioselective beta-blockers (SBBs), reported Susan J. Jordan, PhD, of the University of Queensland School of Public Health in Herston, Australia, and his colleagues.

“Our finding that NSBB supply at the time of first cytoreductive surgery for EOC [epithelial ovarian cancer] was associated with a survival advantage in women aged 50 years and older with a history of CVC was consistent and clinically relevant,” the authors wrote in the Journal of Clinical Oncology. “Two prospective pilot trials investigating perioperative NSBB (propranolol) in ovarian cancer, although small, showed promising results. Large clinical trials are urgently needed, not only to improve survival outcomes, but also to reduce the demand for Health services”.

And they warned that “the reuse of safe and inexpensive drugs, such as propranolol, is impeded by the lack of an immediate financial incentive for private industry to conduct a large randomized clinical trial, so a joint collaborative approach is likely between governments, researchers and funders be required.”

The findings add to a growing body of evidence that NSBBs can improve outcomes in ovarian cancer, said Anil Sood, MD, of the Anderson Center in Houston. Sood, who was not involved in the current study, and his colleagues previously reported similar results in a cohort of patients without CVC.

“We proposed a while back that it’s important to look at the subtypes of beta blockers that are used, selective versus non-selective,” Sood said. medpage today. “In this context, this is an important study because it’s a completely independent group that looked at this issue. They have a considerable number of patients and they worked hard to find out the type of beta-blocker.”

In the large population treated with beta-blockers, patients often receive selective agents that target the beta-1 adrenergic pathway, which “is probably less relevant in the context of tumor biology,” he added. Some studies have focused on beta blockers in general without distinguishing between subtypes. The lack of consideration for drug subtype likely explains the mixed results that have emerged from similar studies, Sood said.

Preclinical studies suggest that catecholamine stimulation of beta-adrenergic receptors increases the synthesis of factors associated with angiogenesis. infantile hemangioma provides indirect clinical evidence that the nonselective beta blocker propranolol, which blocks both beta-1 and beta-2 receptors, has become the standard treatment for benign tumors, the authors noted.

Adrenergic stress before, during, and after surgical resection of tumors can activate inflammatory responses which have been shown to promote tumor growth and increase metastasis in animal models. Surgical stress in mice with transplanted ovarian cancer cells increased tumor activity, which was attenuated by perioperative administration of propranolol.

Human ovarian tumors express beta-2 adrenergic receptors. In vitro studies of human ovarian cells showed that exposure to propranolol induced apoptosis and protective autophagy.

As Sood noted, previous observational studies of perioperative beta-blockade and chemotherapy administration have yielded mixed results. Jordan and his colleagues sought to build on knowledge gained from earlier studies and examine the association between beta-blocker selectivity and survival.

The researchers identified 3,844 Australian women, aged 50 years and older, with a history of CVC and surgery for EOC. At or near the time of surgery, 560 (14.5%) of the patients received SBB and 67 (1.7%) received NSBB. About 85% of patients in the SBB subgroup had hypertension, a quarter had a history of arrhythmia, 18% had heart failure, 95% had ischemic heart disease, and 15% had angina. In the smaller NSBB subgroup, 73% of patients had hypertension and 12% had arrhythmias or heart failure.

Two years after surgery, patients who received NSBB had better OS and CSS compared with patients who did not receive beta-blockers. An analysis of mean causal effects showed that NSBB use was associated with a hazard ratio of 0.47 for all-cause mortality versus no beta-blocker treatment (95% CI: 0.24-0, 94) and an HR of 0.38 for ovarian cancer mortality (95% CI: 0.16-0.93).

In contrast, patients receiving SBB at the time of surgery had 2-year all-cause mortality (HR 1.03, 95% CI 0.89-1.19) and cancer-specific mortality (HR 1.02, 95% CI 0.84-1.25) numerically worse compared to patients not receiving beta-blockers.

The findings have relevance to other cancer types, as noted by the authors of ongoing studies evaluating NSBBs in breast cancer, pancreatic cancerY melanoma. Other research has focused on the effects of beta-2 adrenergic stress on radiotherapy and the ability of NSBBs to reverse adverse effects.

  • Charles Bankhead is a senior oncology editor who also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. To follow

Disclosures

The study was supported by the Australian National Health and Medical Research Council.

Jordan did not disclose any connection to the industry. One co-author disclosed being an employee of Proteomics and a relevant relationship with Zelda Therapeutics.

Sood disclosed relationships with Karyopharm, Roche Diagnostics, GlaxoSmithKline, Merck and AstraZeneca.


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