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
Affiliations
Jennifer M. Knight
Departments of Psychiatry, Medicine, and Microbiology & Immunology, Medical College of Wisconsin
Stephanie A. Kerswill
Medical College of Wisconsin
Parameswaran Hari
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
Steve W. Cole
Department of Medicine, Division of Hematology-Oncology, and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA
Brent R. Logan
Center for International Blood and Marrow Transplant Research; Medical College of Wisconsin
Anita D’Souza
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
Nirav N. Shah
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
Mary M. Horowitz
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
Melinda R. Stolley
Department of Medicine, Medical College of Wisconsin
Erica K. Sloan
Monash Institute of Pharmaceutical Sciences, Monash University
Karen E. Giles
Medical College of Wisconsin
Erin S. Costanzo
Carbone Cancer Center and Department of Psychiatry, University of Wisconsin-Madison
Mehdi Hamadani
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
Saurabh Chhabra
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
Binod Dhakal
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
J. Douglas Rizzo
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin
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.
