ABSTRACT Background Further work is needed to improve treatment outcomes for prostate cancer (PCa), with the repurposing of the α 1 ‐adrenoreceptor antagonists presenting a potential solution. This feasibility clinical trial presents the first prospective data of the use of an α 1 ‐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).
King et al. (Sun,) studied this question.