Repurposing existing medications as cancer therapy: Design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation

Jennifer M. Knight, Stephanie A. Kerswill, Parameswaran Hari, Steve W. Cole, Brent R. Logan, Anita D'Souza, Nirav N. Shah, Mary M. Horowitz, Melinda R. Stolley, Erica K. Sloan, Karen E. Giles, Erin S. Costanzo, Mehdi Hamadani, Saurabh Chhabra, Binod Dhakal, J. Douglas Rizzo

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10 Citations (Scopus)

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.

Original languageEnglish
Article number593
Number of pages12
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - 24 May 2018

Keywords

  • Feasibility
  • Hematopoietic cell transplantation
  • Multiple myeloma
  • Propranolol
  • Repurposed drugs
  • ß-blocker

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