Propranolol for Off-label Treatment of Patients With Melanoma: Results From a Cohort Study.
Vincenzo De Giorgi,Marta Grazzini,Silvia Benemei,Niccolò Marchionni,Edoardo Botteri,Elisabetta Pennacchioli,Pierangelo Geppetti,Sara Gandini +7 more
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TLDR
These results confirm recent observation that propranolol-blockers protect patients with thick cutaneous melanoma from disease recurrence and 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.Abstract:
Importance Preclinical and retrospective studies showed that β-blockers inhibit angiogenesis and disrupt migration of melanoma cells via inhibition of noradrenaline-dependent 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 (80 mg 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 outcome was 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.read more
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References
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Journal ArticleDOI
Propranolol for Severe Hemangiomas of Infancy
Christine Léauté-Labrèze,Dumas de la Roque E,Thomas Hubiche,Franck Boralevi,Thambo Jb,Alain Taieb +5 more
TL;DR: It is observed in 11 children that propranolol can inhibit the growth of infantile capillary hemangiomas and this work is hopeful that this discovery will help improve the prognosis of these patients.
Journal ArticleDOI
The sympathetic nervous system induces a metastatic switch in primary breast cancer.
Erica K. Sloan,Saul J. Priceman,Benjamin F Cox,Stephanie Yu,Matthew A. Pimentel,Veera Tangkanangnukul,Jesusa M.G. Arevalo,Kouki Morizono,Breanne D.W. Karanikolas,Lily Wu,Anil K. Sood,Steven W. Cole +11 more
TL;DR: In this article, the role of neuroendocrine activation in cancer progression was investigated using in vivo bioluminescence imaging to track the development of metastasis in an orthotopic mouse model of breast cancer.
Journal ArticleDOI
Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a β-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor
Ariella Glasner,Roi Avraham,Roi Avraham,Ella Rosenne,Marganit Benish,Oded Zmora,Oded Zmora,Shaily Shemer,Hadas Meiboom,Shamgar Ben-Eliyahu +9 more
TL;DR: Overall, propranolol and etodolac administration, which could be applied perioperatively in most cancer patients with minimal risk and low cost, has counteracted several immunologic and endocrinologic perturbations and improved recurrence-free survival rates in mice undergoing primary tumor excision.
Journal ArticleDOI
Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment
Eddy Pasquier,Joseph Ciccolini,Manon Carré,Sarah Giacometti,Raphaelle Fanciullino,Charlotte Pouchy,Marie-Pierre Montero,Cindy Serdjebi,Maria Kavallaris,Nicolas André +9 more
TL;DR: It is suggested that the use of propranolol concurrently with chemotherapy may improve the outcome of breast cancer patients, thus providing a strong rationale for the evaluation of this drug combination in prospective clinical studies.
Journal ArticleDOI
Treatment with β-blockers and reduced disease progression in patients with thick melanoma.
Vincenzo De Giorgi,Marta Grazzini,Sara Gandini,Silvia Benemei,Torello Lotti,Niccolò Marchionni,Pierangelo Geppetti +6 more
TL;DR: The present study suggests for the first time that exposure to β-blockers for 1 year or more is associated with a reduced risk of progression of thick malignant melanoma, indicating the need for larger epidemiological studies and randomized clinical trials.
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