Enzalutamide Monotherapy with EBRT for Intermediate Risk Prostate Cancer. A Phase 2 Study

Abstract

To assess the efficacy of the anti-androgen, enzalutamide, as short course monotherapy in combination with external beam radiation for intermediate risk. 64 patients were entered into this IRB approved study through the DH/HCC. Patients had biopsy confirmed intermediate risk prostate cancer as defined by a Gleason Score of 7and/or PSA 10-20 and/or T2b/T2c examination. Patients received six 28 day cycles of daily enzalutamide at 120 mg/day. External Beam utilizing IMRT to the prostate and seminal vesicles was begun during the 3rd cycle. Radiation dose was 75.6-79.2Gy in 1.8Gy/fxn. Patients were seen monthly for pill exchange to ensure compliance and end of treatment visit was at 3 months after completion of the enzalutamide (enzalutamide washout). PSA was measured at each visit. In addition levels of several sex hormones and markers of bone metabolism were measured at the beginning of the third and fifth cycle and at the end of treatment. Quality of life questionnaire (EPIC, Pittsburg Sleep inventory. . . . ) were provided and anthropomorphic measures taken at these time points. Fat at biceps, triceps scapula and midriff were measured as well as breast size. Men were permitted to receive external beam to the breast for gynecomastia or mastadynia. The primary endpoint was the PSA level after the 6th cycle of enzalutamide and external beam radiation. The study was powered such that if 60% of patients did not achieve a PSA ≤ 0.2 the study would be negative. Data is available for 62 or 64 patients (2 withdrew consent). In no patient was there a rise in PSA from the nadir during enzalutamide administration. No grade 3 radiation acute toxicities were observed. Grade 3 hypertension was documented in 12% which was managed medically. Significant increases in serum (total) testosterone and estradiol was observed which decreased after discontinuation of the medication. 17 men were treated with breast irradiation due to gynecomastia or mastadynia. There was no significant change in body fat measurements or weight during treatment. There was no change in sleep patterns from baseline during treatment. Use of single agent enzalutamide in combination with external beam radiation was very effective at decreasing PSA to very low levels with minimal toxicity in men with intermediate risk prostate cancer. Breast enlargement/pain and hypertension were the only issues encountered in this study. Further studies are required to determine whether the new class of potent anti-androgens can replace LH-RHa as the hormonal treatment in men with intermediate risk prostate.Abstract 2655; Table 1PSA undetectablePSA ≤0.2ng/mlP ≤0.5ng/mlPSA>0.53849602 Open table in a new tab