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Repurposing existing medications as cancer therapy: design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation. BMC Cancer 2018 May 24;18(1):593 PMID: 29793446 PMCID: PMC5968588

Pubmed ID

29793446

Abstract

BACKGROUND: Repurposing existing medications for antineoplastic purposes can provide a safe, cost-effective, and efficacious means to further augment available cancer care. Clinical and preclinical studies suggest a role for the ß-adrenergic antagonist (ß-blocker) propranolol in reducing rates of tumor progression in both solid and hematologic malignancies. In patients undergoing hematopoietic cell transplantation (HCT), the peri-transplant period is a time of increased activity of the ß-adrenergically-mediated stress response.

METHODS: We conducted a proof-of-concept randomized controlled pilot study assessing the feasibility of propranolol administration to patients between ages 18-75 who received an autologous HCT for multiple myeloma. Feasibility was assessed by enrollment rate, tolerability, adherence, and retention.

RESULTS: One hundred fifty-four patients underwent screening; 31 (20%) enrolled in other oncology trials that precluded dual trial enrollment and 9 (6%) declined to enroll in the current trial. Eighty-nine (58%) did not meet eligibility requirements and 25 (16%) were eligible; of the remaining eligible patients, all were successfully enrolled and randomized. The most common reasons for ineligibility were current ß-blocker use, age, logistics, and medical contraindications. 92% of treatment arm patients tolerated and remained on propranolol for the study duration; 1 patient discontinued due to hypotension. Adherence rate in assessable patients (n = 10) was 94%. Study retention was 100%.

CONCLUSIONS: Findings show that it is feasible to recruit and treat multiple myeloma patients with propranolol during HCT, with the greatest obstacle being other competing oncology trials. These data support further studies examining propranolol and other potentially repurposed drugs in oncology populations.

TRIAL REGISTRATION: This randomized controlled trial was registered at clinicaltrials.gov with the identifier NCT02420223 on April 17, 2015.

Author List

Knight JM, Kerswill SA, Hari P, Cole SW, Logan BR, D'Souza A, Shah NN, Horowitz MM, Stolley MR, Sloan EK, Giles KE, Costanzo ES, Hamadani M, Chhabra S, Dhakal B, Rizzo JD

Authors

Saurabh Chhabra MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Anita D'Souza MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Binod Dhakal MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Jennifer M. Knight MD Assistant Professor in the Psychiatry department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
J. Douglas D. Rizzo MD, MS Director, Ctr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Melinda Stolley PhD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adrenergic beta-Antagonists
Adult
Aged
Chemotherapy, Adjuvant
Disease Progression
Drug Repositioning
Feasibility Studies
Female
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Multiple Myeloma
Patient Compliance
Pilot Projects
Proof of Concept Study
Propranolol
Research Design
Transplantation, Autologous
Treatment Outcome
Young Adult
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6