A phase II study of muscadine grape skin extract in men with biochemically recurrent prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 248-248
Author(s):  
Channing Judith Paller ◽  
Elisabeth I. Heath ◽  
Mary-Ellen Taplin ◽  
Mark N. Stein ◽  
Glenn J. Bubley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Therapeutic Option ◽  
High Dose ◽  
Skin Extract ◽  
Antitumor Effects ◽  
Significant Treatment ◽  
Grape Skin ◽  
Intention To Treat ◽  
Muscadine Grape

248 Background: Pulverized muscadine grape ( Vitis rotundifolia) skin (MPX) is a potential therapeutic option for men with biochemically recurrent (BCR) prostate cancer (PCa) wishing to defer androgen deprivation therapy. MPX demonstrated antitumor effects in PCa through antioxidant activity of its principal polyphenol components, ellagic acid, quercetin, and resveratrol. A Phase I trial demonstrated safety of MPX in doses up to 4000 mg/day. Methods: This is a 12-month, multi-center, placebo-controlled, two-dose, double-blinded trial of MPX (manufactured by Muscadine Naturals Inc. in Warsaw, NC) in 125 men with BCR PCa. Participants were stratified by baseline PSADT and Gleason score, with no restrictions for PSADT and no upper limit PSA value. Patients were randomly assigned 2:2:1 to receive 4000 mg (8 capsules) of MPX, 500 mg (1 capsule) of MPX plus 7 capsules of placebo, or 8 capsules of placebo. PSA levels were obtained every 3 months The trial was powered to detect a statistically significant between-group difference of around 6 months (low dose) and 12 months (high dose) in PSADT relative to placebo. Results: The intention to treat (ITT) population included 116 patients, of which 97% were treated for up to 6 and 58% were treated for up to 12 months. This ITT population was 79% white, with median age 68 years, 47% with Gleason score ≤ 6 or 3+4, and 12% with ECOG status of 1. Median PSADT in the ITT population lengthened from 7.5 months at baseline (range 1.4 to 74.6) to 9.8 months after treatment (range 2.3 to 151.5) (p < 0.001). There was no significant treatment difference in PSADT between the control and the treatment groups (p = 0.84). Eighteen percent (21/116) of men had a post-baseline PSADT of more than 200% of baseline. No clinically significant toxicities were seen. Conclusions: These data suggest that both 500 and 4000 mg of MPX are safe. The lengthening PSADT in patients treated with MPX is not significantly greater than that provided by placebo. A subgroup analysis of patients more likely to benefit (those with the AA genotype of MnSOD) is ongoing. Clinical trial information: NCT01317199.

Inhibition of Prostate Cancer Growth by Muscadine Grape Skin Extract and Resveratrol through Distinct Mechanisms

2007 ◽  
Vol 67 (17) ◽  
pp. 8396-8405 ◽  
Author(s):  
Tamaro S. Hudson ◽  
Diane K. Hartle ◽  
Stephen D. Hursting ◽  
Nomeli P. Nunez ◽  
Thomas T.Y. Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Growth ◽  
Skin Extract ◽  
Grape Skin ◽  
Muscadine Grape ◽  
Grape Skin Extract

A phase I trial of muscadine grape skin in men with biochemically recurrent prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 263-263
Author(s):  
Channing Judith Paller ◽  
Michelle A. Rudek ◽  
Emmanuel S. Antonarakis ◽  
Mario A. Eisenberger ◽  
Hans J. Hammers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
High Dose ◽  
Recurrent Prostate Cancer ◽  
Grape Skin ◽  
Study Results ◽  
Patient Reported ◽  
Muscadine Grape

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.

scholarly journals Val16A SOD2 Polymorphism Promotes Epithelial–Mesenchymal Transition Antagonized by Muscadine Grape Skin Extract in Prostate Cancer Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 213
Author(s):  
Janae D. Sweeney ◽  
Marija Debeljak ◽  
Stacy Riel ◽  
Ana Cecilia Millena ◽  
James R. Eshleman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Skin Extract ◽  
Grape Skin ◽  
Prostate Cell ◽  
Mesenchymal Transition ◽  
Muscadine Grape ◽  
Grape Skin Extract

Epithelial–mesenchymal transition (EMT), a key event in cancer metastasis, allows polarized epithelial cells to assume mesenchymal morphologies, enhancing invasiveness and migration, and can be induced by reactive oxygen species (ROS). Val16A (Ala) SOD2 polymorphism has been associated with increased prostate cancer (PCa) risk. We hypothesized that SOD2 Ala single nucleotide polymorphism (SNP) may promote EMT. We analyzed SOD2 expression and genotype in various prostate cell lines. Stable overexpression of Ala-SOD2 or Val-SOD2 allele was performed in Lymph Node Carcinoma of the Prostate (LNCaP) cells followed by analysis of intracellular ROS and EMT marker protein expression. Treatments were performed with muscadine grape skin extract (MSKE) antioxidant, with or without addition of H2O2 to provide further oxidative stress. Furthermore, MTS cell proliferation, cell migration, and apoptosis assays were completed. The results showed that SOD2 expression did not correlate with tumor aggressiveness nor SOD2 genotype. We demonstrated that the Ala-SOD2 allele was associated with marked induction of EMT indicated by higher Snail and vimentin, lower E-cadherin, and increased cell migration, when compared to Val-SOD2 allele or Neo control cells. Ala-SOD2 SNP cells exhibited increased levels of total ROS and superoxide and were more sensitive to co-treatment with H2O2 and MSKE, which led to reduced cell growth and increased apoptosis. Additionally, MSKE inhibited Ala-SOD2 SNP-mediated EMT. Our data indicates that treatment with a combination of H2O2-generative drugs, such as certain chemotherapeutics and antioxidants such as MSKE that targets superoxide, hold promising therapeutic potential to halt PCa progression in the future.

scholarly journals A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination

The Prostate ◽  
2015 ◽  
Vol 75 (14) ◽  
pp. 1518-1525 ◽  
Author(s):  
Channing J. Paller ◽  
Michelle A. Rudek ◽  
Xian C. Zhou ◽  
William D. Wagner ◽  
Tamaro S. Hudson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Skin Extract ◽  
Recurrent Prostate Cancer ◽  
Grape Skin ◽  
Dose Determination ◽  
Muscadine Grape ◽  
Grape Skin Extract

Results of a Phase II Study Using Estramustine Phosphate and Vinblastine in Combination With High-Dose Three-Dimensional Conformal Radiotherapy for Patients With Locally Advanced Prostate Cancer

2000 ◽  
Vol 18 (9) ◽  
pp. 1936-1941 ◽  
Author(s):  
Michael J. Zelefsky ◽  
William K. Kelly ◽  
Howard I. Scher ◽  
Henry Lee ◽  
Tracy Smart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
High Dose ◽  
Estramustine Phosphate ◽  
Risk Prostate Cancer ◽  
Grade 3 ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

PURPOSE: To assess the feasibility and tolerance of neoadjuvant and concomitant estramustine phosphate and vinblastine (EV) with high-dose three-dimensional conformal radiotherapy (3D-CRT) for patients with unfavorable-risk prostate cancer. PATIENTS AND METHODS: Twenty-seven patients with unfavorable-risk prostate cancer were enrolled onto a prospective study to determine the feasibility of combining EV with 3D-CRT. Patients were eligible if any of the following requirements were satisfied: (1) Gleason score ≥ 8 and prostate-specific antigen (PSA) > 10 ng/mL; (2) Gleason score of 7 and PSA > 20 ng/mL; (3) clinical stage T3N0M0 disease with PSA > 20 ng/mL; (4) any patient with T4N0M0 disease; or (5) patients with TXN1MO disease. Therapy consisted of three 8-week cycles of EV and 8 weeks of 3D-CRT. Estramustine phosphate was given orally beginning on week 1 and continued until the completion of 3D-CRT. Each 8-week cycle of vinblastine consisted of 6 weekly intravenous injections followed by a 2-week rest period. Radiation therapy was administered using a three-dimensional conformal approach to a prescription dose of 75.6 Gy. The median follow-up was 26 months (range, 6 to 40 months). RESULTS: Twenty-three (85%) of 27 patients completed the entire course of therapy and were assessable for toxicities and biochemical outcome. Two patients (7%) developed grade 3 hematologic toxicity that resolved, and two patients (7%) developed grade 3 hepatoxicity, manifesting as persistent elevation of serum transaminase levels, necessitating discontinuation of the chemotherapy and withdrawal from the treatment program. The most prominent adverse effects from this regimen were mild to moderate (grade 1 to 2) nausea and fatigue related to estramustine. Mild peripheral edema was seen in 15% of patients and was treated with diuresis. 3D-CRT was tolerated well in these patients. Medications were required for relief of acute grade 2 rectal (gastrointestinal [GI]) and urinary (genitourinary [GU]) symptoms in 35% and 48% of patients, respectively. Three patients developed acute grade 3 GU toxicities. The 2-year actuarial likelihood of late grade 2 GI toxicity was 20%. No late grade 3 or 4 GI toxicities were observed. The 2-year actuarial likelihoods of late grade 2 and 3 GU toxicities were 25% and 12%, respectively. No grade 4 GU toxicity was observed. CONCLUSION: Neoadjuvant and concomitant EV with high-dose 3D-CRT is well tolerated in patients with unfavorable-risk prostate cancer. Although the incidence of modest (grade 2) late GI and GU toxicities seem to be increased compared with 3D-CRT alone or in combination with androgen ablation therapy, no severe toxicities were encountered with this regimen.

A phase II study of pomegranate extract for men with rising prostate-specific antigen following primary therapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 11-11 ◽  
Author(s):  
M. A. Carducci ◽  
C. J. Paller ◽  
P. Wozniak ◽  
P. Sieber ◽  
R. Greengold ◽  
...  
Keyword(s):  
Gleason Score ◽  
Phase Ii ◽  
Specific Antigen ◽  
Local Therapy ◽  
Pomegranate Juice ◽  
Primary Therapy ◽  
Antitumor Effects ◽  
Significant Treatment ◽  
Clinically Significant ◽  
Intent To Treat

11 Background: Pomegranate extract (POMx) demonstrates promising antitumor effects in prostate cancer (PCA). Prior published work reveals an increase in PSA doubling time (PSADT) in a single arm study of pomegranate juice (POM) in PCA patients (pts) with a rising PSA after local therapy. We sought to determine the effects of low (1 gram) or high (3 grams) daily POMx on PSADT in a similar but broader population of men seeking to defer androgen deprivation therapy. Methods: Our multi-center, double bind phase II trial randomized men with rising PSA and without metastases to receive high or low dose POMx, stratified by baseline PSADT and Gleason score, and with no restrictions for PSADT and no upper limit PSA value. Men were treated until progression or for 18 months. PSA levels were obtained every 3 months. This study was designed to detect a 6 month increase in PSADT from baseline. Results: 104 patients were enrolled and treated for up to 6 (92%), 12 (70%) and 18 months (36%). Median PSADT lengthened in the Intent to treat population (96% white, median age 74.5 years, median Gleason score 7) from baseline 11.9 (range 1.6-54.6) compared to 18.5 (2-1523) months after treatment (p<.001).There was no significant treatment difference on PSADT between the dose groups (p=.920). Declining PSA levels were observed in 13 pts (13%) during the study. No significant changes occurred in testosterone in either group. Although no clinically significant toxicities were seen, mild to moderate diarrhea was seen in 8 pts (7.7%). Conclusions: POMx treatment significantly increased the PSADT by over 6 months in both treatment arms, with no effect on testosterone. This IND-conducted study confirms slowing of PSADT after treatment with POMx as was found with POM, yet in a PCA patient population with greater high risk progression features. [Table: see text]

Potential predictive and prognostic factors for sequential treatment with abiraterone acetate and cabazitaxel in metastatic docetaxel-refractory castration-resistant prostate cancer (mDR-CRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16093-e16093
Author(s):  
Sergio Bracarda ◽  
Alketa Hamzaj ◽  
Michele Sisani ◽  
Giuseppe Di Lorenzo ◽  
Francesca Marrocolo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Gleason Score ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Activity Data ◽  
Intention To Treat ◽  
Group 2 ◽  
Ecog Ps

e16093 Background: in recent years Abiraterone Acetate (AA) andCabazitaxel (Cbz) were shown to be efficacious agents in patients with mDR-CRPC. However, no data exist for patients treated with both these drugs in terms of best sequencing evaluation and potential predictive and prognostic factors for different treatment sequencies. Aim of our study was to analyze these data in a real world scenario. Methods: intention-to-treat (ITT) analysis of activity data deriving from all consecutive patients with mDR-CRPC treated in our unit with prednisone plus Cbz, AA or both drugs. Data analyzed were, median Progression Free Survival (mPFS) for the two single agents and their sequencies (evaluated according to PCWG2, Prostate Cancer Working Group 2, criteria) and their possible correlations with median age, Gleason score, baseline PSA, ECOG PS, visceral metastases and number of previous chemotherapy lines. Results: here we report characteristics and activity data of the initial 62 patients, 7 treated with Cbz, 32 with AA and 16 with both drugs. The median age of our study population was 71.5 years (range, 55-87), median Gleason Score 8 (4-9) and median ECOG PS 0 (0–3); visceral disease was present in 37 cases (59.7%). The mPFS, according to Kaplan Meier method (KM), was 4.7 months (m) for patients treated with Cbz, 8.6 months for cases treated with AA and 8.2 m for cases treated with both agents. Of the 16 patients treated with both drugs, 12 received a sequence Cbz-AA and 4 a sequence AA-Cbz for an overall median PFS of, respectively, 5.6 and 4.0 m. Any of the analyzed prognostic or predictive factor was found to be significant. Conclusions: in our experience AA and Cbz were showed to be effective agents in the mDR-CRPC setting also when used sequentially. No clear indication of a preferred treatment sequence was identified such as eventual prognostic/predictive factors, also because of the limited number of treated patients. These data should be analyzed in large size prospective trials.

scholarly journals Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells

2015 ◽  
Vol 36 (9) ◽  
pp. 1019-1027 ◽  
Author(s):  
Liza J. Burton ◽  
Basil A. Smith ◽  
Bethany N. Smith ◽  
Quentin Loyd ◽  
Peri Nagappan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cathepsin L ◽  
Skin Extract ◽  
Grape Skin ◽  
Muscadine Grape ◽  
Grape Skin Extract
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