Off-Label Propranolol Reduces Melanoma Recurrence

The off-label use of the beta-blocker propranolol significantly reduced disease recurrence among patients with non-metastatic melanoma, according to the results of a prospective, non-randomized study published as a brief report in JAMA Oncology.

“This study is the first we know of to evaluate the administration of a beta-blocker to patients as adjuvant therapy at the time of diagnosis of melanoma,” wrote Vincenzo De Giorgi, MD, of the University of Florence, Italy, and colleagues. “These results provide the basis for larger trials of longer duration to measure the clinical efficacy of propranolol.”

The prospective study included patients with histologically confirmed stage IB to IIIA cutaneous melanoma without metastasis. Patients were asked to take propranolol 80 mg daily. Those who accepted were part of the propranolol arm (PROP; n = 19); those who agreed to participate in the study but not to take propranolol were part of the non-propranolol arm (No-PROP; n = 34).

The two arms were well balanced except that the PROP arm had more cases of ulcerated melanoma, which the researchers noted presents a greater risk for disease progression.

After a median follow-up of 3 years, 41.2% of patients in the No-PROP arm had disease progression compared with 15.8% of patients in the PROP arm. The 3-year disease-free survival was 89% in the PROP arm compared with 64% in the No-PROP arm (P = .04).

Adjusted analyses showed an 80% risk reduction for recurrence when propranolol was used from the time of diagnosis (hazard ratio, 0.18; 95% CI, 0.04–0.89; P = .03).

“This result is important because in the propranolol cohort histopathological examinations showed a greater number of cases with ulceration, which is considered a poor prognostic factor,” the researchers wrote. “Even overall survival, although not significant, showed a trend toward decreased mortality in the propranolol group after 3 years of follow-up.”

There were no adverse events in the PROP group.

The researchers acknowledged that the study has limitations including the small sample size and its prospective nature.

“The development of randomized placebo-controlled clinical trials is necessary to clarify a definitive role for beta-blockers in protecting against the risk of progression of melanoma and to potentially identify the receptor subtype involved in the protective effect,” the wrote.