Muscadine grape skin extract (MPX) in men with biochemically recurrent prostate cancer: A randomized, multicenter, placebo-controlled clinical trial

Channing J. Paller, Xian C. Zhou, Elisabeth I. Heath, Mary Ellen Taplin, Tina Mayer, Mark N. Stein, Glenn J. Bubley, Roberto Pili, Tamaro Hudson, Radhika Kakarla, Muneer M. Abbas, Nicole M. Anders, Donna Dowling, Serina King, Ashley B. Bruns, William D. Wagner, Charles G. Drake, Emmanuel S. Antonarakis, Mario A. Eisenberger, Samuel R. DenmeadeMichelle A. Rudek, Gary L. Rosner, Michael A. Carducci

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)306-315
Number of pages10
JournalClinical Cancer Research
Volume24
Issue number2
DOIs
StatePublished - Jan 15 2018
Externally publishedYes

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Controlled Clinical Trials
Vitis
Prostatic Neoplasms
Placebos
Skin
Alanine
Genotype
Neoplasm Grading
Polyphenols
Therapeutics
Lipid Peroxidation
Population
Androgens
Research Design
Pharmacokinetics
Pharmaceutical Preparations
superoxide dismutase 2

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 journalArticle

Paller, CJ, Zhou, XC, Heath, EI, Taplin, ME, Mayer, T, Stein, MN, Bubley, GJ, Pili, R, Hudson, T, Kakarla, R, Abbas, MM, Anders, NM, Dowling, D, King, S, Bruns, AB, Wagner, WD, Drake, CG, Antonarakis, ES, Eisenberger, MA, Denmeade, SR, Rudek, MA, Rosner, GL & Carducci, MA 2018, 'Muscadine grape skin extract (MPX) in men with biochemically recurrent prostate cancer: A randomized, multicenter, placebo-controlled clinical trial', Clinical Cancer Research, vol. 24, no. 2, pp. 306-315. https://doi.org/10.1158/1078-0432.CCR-17-1100
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. / Muscadine grape skin extract (MPX) in men with biochemically recurrent prostate cancer : A randomized, multicenter, placebo-controlled clinical trial. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 2. pp. 306-315.
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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.",
author = "Paller, {Channing J.} and Zhou, {Xian C.} and Heath, {Elisabeth I.} and Taplin, {Mary Ellen} and Tina Mayer and Stein, {Mark N.} and Bubley, {Glenn J.} and Roberto Pili and Tamaro Hudson and Radhika Kakarla and Abbas, {Muneer M.} and Anders, {Nicole M.} and Donna Dowling and Serina King and Bruns, {Ashley B.} and Wagner, {William D.} and Drake, {Charles G.} and Antonarakis, {Emmanuel S.} and Eisenberger, {Mario A.} and Denmeade, {Samuel R.} and Rudek, {Michelle A.} and Rosner, {Gary L.} and Carducci, {Michael A.}",
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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.

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