263 Background: New therapies are being explored as an alternative to observation in men with biochemically recurrent prostate cancer (BRPC). Muscadine Grape Skin (MPX) is comprised of ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro. Here we summarize data from a phase I dose finding trial. Methods: This phase I study assigned non-metastatic BRPC patients to increasing doses of MPX (Muscadine Naturals) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Dose selection is based on preclinical data showing the equivalent of 500 to 4,000 mg of MPX to be safe in mouse models. Our primary end point was to determine the recommended phase II dosing. We calculated changes in prostate-specific antigen (PSA) doubling time (PSADT) from at least three measurements prior to trial initiation and PSA measurements on study. Results: The cohort (n=14, 71% white, 29% black) had a median follow-up of 14.7 (6.9 to 20.7) months, median age 61, median Gleason seven, and median PSA of 5.1 ng/mL (0.2 to 153.4). Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 burping. No other related adverse events were reported and one patient reported improvement of chronic constipation. Two of 14 patients came off study for metastatic disease. Median within-patient PSADT increased from 9.4 to 12.3 months with a PSADT difference of 3.9 months. Conclusions: These data suggest that 4,000 mg of MPX is safe, and exploratory review of change in PSADT suggests there is enough data to proceed to a phase II trial. Both low dose (500 mg) and high dose (4,000 mg) MPX are being further investigated in a multicenter, placebo-controlled, dose evaluating phase II trial. Clinical trial information: NCT01317199.
Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial