A phase II study of degarelix prior to radiation on prostatic tissue androgens.

Abstract

103 Background: Optimizing androgen suppression may provide better treatment outcomes for localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation (ADT) with definitive radiotherapy in men with locally advanced or high-grade disease. LHRH agonist (LHRHa) is most commonly used. The LHRH antagonist degarelix may provide more robust androgen suppression. The impact on tissue androgens following use of degarelix prior to radiation has not been reported. We examined the impact on androgens in serum and tissue after 12 weeks of degarelix in this phase II study. Methods: A prospective, phase II study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent degarelix with radiation. Prostate biopsies were obtained at the time of fiducial placement before radiotherapy. Serum and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Needle biopsies from a separate analysis of untreated men or those receiving LHRHa prior to prostatectomy were used as tissue androgen level controls. Results: 16 men with intermediate (4) and high-risk (12) PCa received study therapy. 14 men completed degarelix and planned radiation to 77.4-81 Gy. Serum and tissue androgens after 12 weeks of therapy are compared to untreated control and LHRHa treated patients (12 weeks). Serum levels of dihydrotestosterone (DHT) and testosterone were similarly suppressed by LHRHa or degarelix compared to untreated controls, without statistically significant differences. Degarelix provided statistically greater reduction in androsterone than LHRHa. Conclusions: In this phase II study degarelix and LHRHa achieved similar serum and tissue androgen levels at 12 weeks; however, there was a greater suppression of tissue androsterone with degarelix. The clinical significance of this difference remains uncertain. Clinical trial information: NCT01731912. [Table: see text]