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Published on: March 6, 2018
A Feasibility Study of the Repurposing of Prazosin to Improve Treatment Outcomes in Men Receiving Radiotherapy for
Liam D King1, David Christie1,2, Daniel Cehic3,4
1School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Queensland, Australia.
Background:
Further work is needed to improve treatment outcomes for prostate cancer (PCa), with the repurposing of the α1-adrenoreceptor antagonists presenting a potential solution. This feasibility clinical trial presents the first prospective data of the use of an α1-adrenoreceptor antagonist in men undergoing radiotherapy for PCa.
Methods:
The study enrolled men planned to receive radiotherapy for PCa. Participants received escalating doses of prazosin administered during radiotherapy. Blood pressure was recorded at each radiotherapy fraction. The primary outcome was treatment protocol feasibility and secondary outcomes were maximum tolerated dose (MTD) of prazosin, safety, and progression-free survival (PFS).
Results:
Ten participants were enrolled into the study and all achieved > 90% treatment compliance and > 80% assessment compliance. One participant and four participants achieved an MTD of 1 mg and 0.5 mg, respectively, and the remaining five participants had an MTD of 0 mg, with the overall protocol defined MTD being 0 mg. There were no Grades 3/4 adverse events. All treatment-related adverse events (TRAE) were either hypotension or orthostatic hypotension, of the 17 reported TRAEs 16 were asymptomatic. No participants had evidence of disease progression at the 36-week follow-up.
Conclusions:
Our study demonstrated that coadministration of prazosin during radiotherapy is feasible. However, the incidence of hypotension resulted in a protocol-defined MTD (under conservative blood pressure based DLT definition) of 0 mg, although 16 of the 17 reports were asymptomatic. Combined with monitoring used in other studies utilizing prazosin, this suggests that our safety monitoring and dose-limiting toxicity (DLT) definition may have been too strict and did not accurately reflect a clinically relevant MTD. As this study achieved its primary aim and demonstrated the feasibility of the administration of prazosin during radiotherapy, further prospective studies are justified, with greater consideration given to the definition of DLTs.
Trial Registration:
Australian New Zealand Clinical Trials Registry (381954).
Insights
This study found that giving prazosin during prostate cancer (PCa) radiotherapy was feasible. While hypotension occurred, most cases were asymptomatic, suggesting further trials with refined safety measures are warranted.
Area of Science:
- Oncology
- Pharmacology
- Radiotherapy
Background:
- Improving prostate cancer (PCa) treatment outcomes is crucial.
- Repurposing alpha1-adrenoreceptor antagonists offers a potential therapeutic avenue.
- This study provides the first prospective data on using an alpha1-adrenoreceptor antagonist during PCa radiotherapy.
Purpose of the Study:
- To assess the feasibility of administering prazosin concurrently with radiotherapy in men with PCa.
- To determine the maximum tolerated dose (MTD), safety profile, and progression-free survival (PFS) of prazosin during PCa radiotherapy.
Main Methods:
- A feasibility clinical trial involving men undergoing radiotherapy for PCa.
- Escalating doses of prazosin were administered during radiotherapy sessions.
- Blood pressure monitoring, MTD assessment, safety evaluation, and PFS were primary and secondary outcomes.
Main Results:
- Ten participants completed the study with high compliance rates.
- The protocol-defined MTD of prazosin was 0 mg due to hypotension, although most adverse events were asymptomatic.
- No Grade 3/4 adverse events were reported, and no participants showed disease progression at 36 weeks.
Conclusions:
- Coadministration of prazosin during PCa radiotherapy is feasible.
- The strict definition of dose-limiting toxicity (DLT) may have underestimated the clinically relevant MTD.
- Further prospective studies are recommended, with careful consideration of DLT definitions for prazosin in PCa radiotherapy.
