TY - JOUR
T1 - A phase i study of muscadine grape skin extract in men with biochemically recurrent prostate cancer
T2 - Safety, tolerability, and dose determination
AU - Paller, Channing J.
AU - Rudek, Michelle A.
AU - Zhou, Xian C.
AU - Wagner, William D.
AU - Hudson, Tamaro S.
AU - Anders, Nicole
AU - Hammers, Hans J.
AU - Dowling, Donna
AU - King, Serina
AU - Antonarakis, Emmanuel S.
AU - Drake, Charles G.
AU - Eisenberger, Mario A.
AU - Denmeade, Samuel R.
AU - Rosner, Gary L.
AU - Carducci, Michael A.
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - BACKGROUND New therapies are being explored as therapeutic options for men with biochemically recurrent prostate cancer (BRPC) who wish to defer androgen deprivation therapy. MPX is pulverized muscadine grape (Vitis rotundifolia) skin that contains ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro. METHODS In the phase I portion of this phase I/II study, non-metastatic BRPC patients were assigned to increasing doses of MPX (Muscadine Naturals. Inc., Clemmons, NC) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Initial dose selection was based on preclinical data showing the equivalent of 500 to 4,000mg of MPX to be safe in mouse models. The primary endpoint was the recommended phase II dosing regimen. RESULTS The cohort (n=14, 71% Caucasian, 29% black) had a median follow-up of 19.2 (6.2-29.7) months, median age of 61 years, and median Gleason score of 7. Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 eructation. No other related adverse events were reported and one patient reported improvement of chronic constipation. Six of 14 patients came off study for disease progression (five metastatic, one rising PSA) after exposure for a median of 15 months. One patient came off for myasthenia gravis that was unrelated to treatment. Seven patients remain on study. The lack of dose-limiting toxicities led to the selection of 4,000mg/d as the highest dose for further study. Median within-patient PSADT increased by 5.3 months (non-significant, P=0.17). No patients experienced a maintained decline in serum PSA from baseline. CONCLUSION These data suggest that 4,000mg of MPX is safe, and exploratory review of a lengthening in PSADT of a median of 5.3 months supports further exploration of MPX. Both low-dose (500mg) and high-dose (4,000mg) MPX are being further investigated in a randomized, multicenter, placebo-controlled, dose-evaluating phase II trial. Prostate 75:1518-1525, 2015.
AB - BACKGROUND New therapies are being explored as therapeutic options for men with biochemically recurrent prostate cancer (BRPC) who wish to defer androgen deprivation therapy. MPX is pulverized muscadine grape (Vitis rotundifolia) skin that contains ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro. METHODS In the phase I portion of this phase I/II study, non-metastatic BRPC patients were assigned to increasing doses of MPX (Muscadine Naturals. Inc., Clemmons, NC) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Initial dose selection was based on preclinical data showing the equivalent of 500 to 4,000mg of MPX to be safe in mouse models. The primary endpoint was the recommended phase II dosing regimen. RESULTS The cohort (n=14, 71% Caucasian, 29% black) had a median follow-up of 19.2 (6.2-29.7) months, median age of 61 years, and median Gleason score of 7. Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 eructation. No other related adverse events were reported and one patient reported improvement of chronic constipation. Six of 14 patients came off study for disease progression (five metastatic, one rising PSA) after exposure for a median of 15 months. One patient came off for myasthenia gravis that was unrelated to treatment. Seven patients remain on study. The lack of dose-limiting toxicities led to the selection of 4,000mg/d as the highest dose for further study. Median within-patient PSADT increased by 5.3 months (non-significant, P=0.17). No patients experienced a maintained decline in serum PSA from baseline. CONCLUSION These data suggest that 4,000mg of MPX is safe, and exploratory review of a lengthening in PSADT of a median of 5.3 months supports further exploration of MPX. Both low-dose (500mg) and high-dose (4,000mg) MPX are being further investigated in a randomized, multicenter, placebo-controlled, dose-evaluating phase II trial. Prostate 75:1518-1525, 2015.
KW - PSADT
KW - complementary therapy
KW - muscadine grape skin
KW - prostate cancer
KW - rising PSA
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U2 - 10.1002/pros.23024
DO - 10.1002/pros.23024
M3 - Article
C2 - 26012728
AN - SCOPUS:84939207788
SN - 0270-4137
VL - 75
SP - 1518
EP - 1525
JO - Prostate
JF - Prostate
IS - 14
ER -