Abstract
Purpose: MuscadinePlus (MPX), a commercial preparation of pulverized muscadine grape skin, was evaluated as a therapeutic option for men with biochemically recurrent (BCR) prostate cancer wishing to defer androgen deprivation therapy. Experimental Design: This was a 12-month, multicenter, placebo-controlled, two-dose, double-blinded trial of MPX in 125 men with BCR prostate cancer, powered to detect a PSA doubling time (PSADT) difference of 6 months (low dose) and 12 months (high dose) relative to placebo. Participants were stratified (baseline PSADT, Gleason score) and randomly assigned 1:2:2 to receive placebo, 500 mg MPX (low), or 4, 000 mg MPX (high) daily. Correlates included superoxide dismutase-2 (SOD2) genotype, lipid peroxidation, and polyphenol pharmacokinetics. Results: The evaluable population included 112 patients, all treated for at least 6 months and 62% treated for 12 months. No significant difference was found in PSADT change between control and treatment arms (P = 0.81): control 0.9 months (n = 20; range, 6.7-83.1), low dose 1.5 months (n=52; range, 10.3-87.2), high dose 0.9 months (n = 40; range, 27.3-88.1). One high-dose patient experienced objective response. No drug-related CTCAE grade 3-4 adverse events were seen. In a preplanned exploratory analysis, PSADT pre-to-post increase was significant in the 27 (26%) genotyped patients with SOD2 Alanine/Alanine genotype (rs4880 T>C polymorphism) on MPX (pooled treatment arms; 6.4 months, P = 0.02), but not in control (1.8 months, P = 0.25). Conclusions: Compared with placebo, MPX did not significantly prolong PSADT in BCR patients over two different doses. Exploratory analysis revealed a patient population with potential benefit that would require further study.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 306-315 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 24 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2018 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Muscadine grape skin extract (MPX) in men with biochemically recurrent prostate cancer : A randomized, multicenter, placebo-controlled clinical trial. / Paller, Channing J.; Zhou, Xian C.; Heath, Elisabeth I.; Taplin, Mary Ellen; Mayer, Tina; Stein, Mark N.; Bubley, Glenn J.; Pili, Roberto; Hudson, Tamaro; Kakarla, Radhika; Abbas, Muneer M.; Anders, Nicole M.; Dowling, Donna; King, Serina; Bruns, Ashley B.; Wagner, William D.; Drake, Charles G.; Antonarakis, Emmanuel S.; Eisenberger, Mario A.; Denmeade, Samuel R.; Rudek, Michelle A.; Rosner, Gary L.; Carducci, Michael A.
In: Clinical Cancer Research, Vol. 24, No. 2, 15.01.2018, p. 306-315.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Muscadine grape skin extract (MPX) in men with biochemically recurrent prostate cancer
T2 - A randomized, multicenter, placebo-controlled clinical trial
AU - Paller, Channing J.
AU - Zhou, Xian C.
AU - Heath, Elisabeth I.
AU - Taplin, Mary Ellen
AU - Mayer, Tina
AU - Stein, Mark N.
AU - Bubley, Glenn J.
AU - Pili, Roberto
AU - Hudson, Tamaro
AU - Kakarla, Radhika
AU - Abbas, Muneer M.
AU - Anders, Nicole M.
AU - Dowling, Donna
AU - King, Serina
AU - Bruns, Ashley B.
AU - Wagner, William D.
AU - Drake, Charles G.
AU - Antonarakis, Emmanuel S.
AU - Eisenberger, Mario A.
AU - Denmeade, Samuel R.
AU - Rudek, Michelle A.
AU - Rosner, Gary L.
AU - Carducci, Michael A.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - Purpose: MuscadinePlus (MPX), a commercial preparation of pulverized muscadine grape skin, was evaluated as a therapeutic option for men with biochemically recurrent (BCR) prostate cancer wishing to defer androgen deprivation therapy. Experimental Design: This was a 12-month, multicenter, placebo-controlled, two-dose, double-blinded trial of MPX in 125 men with BCR prostate cancer, powered to detect a PSA doubling time (PSADT) difference of 6 months (low dose) and 12 months (high dose) relative to placebo. Participants were stratified (baseline PSADT, Gleason score) and randomly assigned 1:2:2 to receive placebo, 500 mg MPX (low), or 4, 000 mg MPX (high) daily. Correlates included superoxide dismutase-2 (SOD2) genotype, lipid peroxidation, and polyphenol pharmacokinetics. Results: The evaluable population included 112 patients, all treated for at least 6 months and 62% treated for 12 months. No significant difference was found in PSADT change between control and treatment arms (P = 0.81): control 0.9 months (n = 20; range, 6.7-83.1), low dose 1.5 months (n=52; range, 10.3-87.2), high dose 0.9 months (n = 40; range, 27.3-88.1). One high-dose patient experienced objective response. No drug-related CTCAE grade 3-4 adverse events were seen. In a preplanned exploratory analysis, PSADT pre-to-post increase was significant in the 27 (26%) genotyped patients with SOD2 Alanine/Alanine genotype (rs4880 T>C polymorphism) on MPX (pooled treatment arms; 6.4 months, P = 0.02), but not in control (1.8 months, P = 0.25). Conclusions: Compared with placebo, MPX did not significantly prolong PSADT in BCR patients over two different doses. Exploratory analysis revealed a patient population with potential benefit that would require further study.
AB - Purpose: MuscadinePlus (MPX), a commercial preparation of pulverized muscadine grape skin, was evaluated as a therapeutic option for men with biochemically recurrent (BCR) prostate cancer wishing to defer androgen deprivation therapy. Experimental Design: This was a 12-month, multicenter, placebo-controlled, two-dose, double-blinded trial of MPX in 125 men with BCR prostate cancer, powered to detect a PSA doubling time (PSADT) difference of 6 months (low dose) and 12 months (high dose) relative to placebo. Participants were stratified (baseline PSADT, Gleason score) and randomly assigned 1:2:2 to receive placebo, 500 mg MPX (low), or 4, 000 mg MPX (high) daily. Correlates included superoxide dismutase-2 (SOD2) genotype, lipid peroxidation, and polyphenol pharmacokinetics. Results: The evaluable population included 112 patients, all treated for at least 6 months and 62% treated for 12 months. No significant difference was found in PSADT change between control and treatment arms (P = 0.81): control 0.9 months (n = 20; range, 6.7-83.1), low dose 1.5 months (n=52; range, 10.3-87.2), high dose 0.9 months (n = 40; range, 27.3-88.1). One high-dose patient experienced objective response. No drug-related CTCAE grade 3-4 adverse events were seen. In a preplanned exploratory analysis, PSADT pre-to-post increase was significant in the 27 (26%) genotyped patients with SOD2 Alanine/Alanine genotype (rs4880 T>C polymorphism) on MPX (pooled treatment arms; 6.4 months, P = 0.02), but not in control (1.8 months, P = 0.25). Conclusions: Compared with placebo, MPX did not significantly prolong PSADT in BCR patients over two different doses. Exploratory analysis revealed a patient population with potential benefit that would require further study.
UR - http://www.scopus.com/inward/record.url?scp=85040718932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040718932&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-17-1100
DO - 10.1158/1078-0432.CCR-17-1100
M3 - Article
C2 - 29113986
AN - SCOPUS:85040718932
VL - 24
SP - 306
EP - 315
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 2
ER -