Phase II study of neoadjuvant 'supercastration' in men with high-risk prostate cancer.

Abstract

Introduction: Men with high-risk prostate cancer are at increased risk of disease relapse post-prostatectomy. Previous neo-adjuvant studies demonstrate reductions in positive margin rates, but a low pT0 response rate and no improvement in biochemical recurrence-free survival. With the advent of more effective hormonal agents we wished to determine if a ‘supercastration’ combination led to an increased pT0 response rate compared to historical controls.

Patients and Methods: This is an open label non-randomised Phase II study neoadjuvant study of ‘supercastration’ in men with high-risk clinically localized prostate cancer. Treatment consists of Degarelix 240/80 mg q 1/12, Abiraterone 1000 mg OD, Bicalutamide 50 mg OD and Prednisolone 5 mg OD for 24 weeks. The primary endpoints are safety/tolerability and pT0 response rate. Secondary endpoints include correlative molecular and hormonal studies. Using an optimal 2-stage design, the trial is powered to detect a pT0 response rate of 25%, with at least one pT0 response required in the first 9 patients required to trigger recruitment to the second phase. The final anticipated sample size is 12–17.

Results: To date 13 patients have been recruited. The combination treatment has been well tolerated, with hot flushes and fatigue being the most commonly reported side effects. Three patients with asymptomatic elevation of liver transaminases required Abiraterone dose reductions, and there have been no unexpected toxicities. One patient in the first phase had a complete pathological response, with complete resolution of high-grade disease observed in a second patient.

Conclusions: This ongoing Phase II trial will offer insights into the role of neoadjuvant ‘supercastration’ in men with high-risk prostate cancer. Correlative molecular studies will be performed to elucidate molecular mechanisms of resistance in persistent tumour tissue.