TY - JOUR
T1 - Propranolol for off-label treatment of patients with melanoma
T2 - Results from a cohort study
AU - De Giorgi, Vincenzo
AU - Grazzini, Marta
AU - Benemei, Silvia
AU - Marchionni, Niccolo
AU - Botteri, Edoardo
AU - Pennacchioli, Elisabetta
AU - Geppetti, Pierangelo
AU - Gandini, Sara
PY - 2018/2/1
Y1 - 2018/2/1
N2 - IMPORTANCE: Preclinical and retrospective studies showed that β-blockers inhibit angiogenesis and disrupt migration of melanoma cells via inhibition of noradrenalinedependent responses. OBJECTIVE: To study the clinical effectiveness of β-blocker therapy in patients with melanoma and to determine whether propranolol improves progression-free survival in patients with melanoma. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective study in patients treated for melanoma in our center with propranolol for off-label use. Patients with histologically confirmed stage IB to IIIA cutaneous melanoma and no evidence of metastasis were eligible for the study. At the time of diagnosis, they were asked to take propranolol (80mg daily) as an off-label adjuvant treatment. If they accepted the treatment, they were considered part of the propranolol cohort (PROP). If they refused treatment but agreed to participate in the study control group, they were considered part of the nonpropranolol cohort (No-PROP). MAIN OUTCOMES AND MEASURES: The primary outcomewas progression-free survival. Disease progression was assessed by evaluating the presence of lymphatic, in-transit, or visceral metastases, and the cause of death was recorded. RESULTS: Among the 53 patients (median [interquartile range] age 63 [48-75] years; 33 men) included in the study, 19 were eligible for the PROP cohort. Thirty-four patients otherwise eligible but unwilling to take propranolol were enrolled in the No-PROP cohort. The 2 cohorts were comparable in terms of demographic characteristics and primary prognostic factors at baseline. After adjusting for known prognostic factors, Cox models confirmed that use of propranolol at the time of diagnosis was significantly inversely associated with recurrence of melanoma with approximately an 80% risk reduction for propranolol users (hazard ratio, 0.18; 95%CI, 0.04-0.89; P = .03). CONCLUSIONS AND RELEVANCE: In the absence of randomized, double-blind, placebo-controlled clinical trials, this study is the first off-label study of which we are aware of propranolol for melanoma treatment. These results confirm recent observation that β-blockers protect patients with thick cutaneous melanoma from disease recurrence. This study is in accordance with the present policy of "drug repurposing" in oncology. Repurposing the vast arsenal of approved drugs with a nononcology primary purpose may prove an attractive and inexpensive strategy for offering more effective treatment options to patients with cancer.
AB - IMPORTANCE: Preclinical and retrospective studies showed that β-blockers inhibit angiogenesis and disrupt migration of melanoma cells via inhibition of noradrenalinedependent responses. OBJECTIVE: To study the clinical effectiveness of β-blocker therapy in patients with melanoma and to determine whether propranolol improves progression-free survival in patients with melanoma. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective study in patients treated for melanoma in our center with propranolol for off-label use. Patients with histologically confirmed stage IB to IIIA cutaneous melanoma and no evidence of metastasis were eligible for the study. At the time of diagnosis, they were asked to take propranolol (80mg daily) as an off-label adjuvant treatment. If they accepted the treatment, they were considered part of the propranolol cohort (PROP). If they refused treatment but agreed to participate in the study control group, they were considered part of the nonpropranolol cohort (No-PROP). MAIN OUTCOMES AND MEASURES: The primary outcomewas progression-free survival. Disease progression was assessed by evaluating the presence of lymphatic, in-transit, or visceral metastases, and the cause of death was recorded. RESULTS: Among the 53 patients (median [interquartile range] age 63 [48-75] years; 33 men) included in the study, 19 were eligible for the PROP cohort. Thirty-four patients otherwise eligible but unwilling to take propranolol were enrolled in the No-PROP cohort. The 2 cohorts were comparable in terms of demographic characteristics and primary prognostic factors at baseline. After adjusting for known prognostic factors, Cox models confirmed that use of propranolol at the time of diagnosis was significantly inversely associated with recurrence of melanoma with approximately an 80% risk reduction for propranolol users (hazard ratio, 0.18; 95%CI, 0.04-0.89; P = .03). CONCLUSIONS AND RELEVANCE: In the absence of randomized, double-blind, placebo-controlled clinical trials, this study is the first off-label study of which we are aware of propranolol for melanoma treatment. These results confirm recent observation that β-blockers protect patients with thick cutaneous melanoma from disease recurrence. This study is in accordance with the present policy of "drug repurposing" in oncology. Repurposing the vast arsenal of approved drugs with a nononcology primary purpose may prove an attractive and inexpensive strategy for offering more effective treatment options to patients with cancer.
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U2 - 10.1001/jamaoncol.2017.2908
DO - 10.1001/jamaoncol.2017.2908
M3 - Article
AN - SCOPUS:85044624180
VL - 4
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 2
M1 - e172908
ER -