Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.
OBJECTIVE
Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy.


METHODS
A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels.


RESULTS
The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption.


CONCLUSIONS
We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.
Pantuck
Allan J
AJ
Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1738, USA. apantuck@mednet.ucla.edu
Leppert
John T
JT
Zomorodian
Nazy
N
Aronson
William
W
Hong
Jenny
J
Barnard
R James
RJ
Seeram
Navindra
N
Liker
Harley
H
Wang
Hejing
H
Elashoff
Robert
R
Heber
David
D
Aviram
Michael
M
Ignarro
Louis
L
Belldegrun
Arie
A
D000284:Administration, Oral; D017209:Apoptosis / Q000187:drug effects; D001628:Beverages; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D008055:Lipids / Q000097:blood; D029561:Lythraceae; D008297:Male; D017942:Nitric Acid / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D008055:Lipids; D028321:Plant Preparations; D017942:Nitric Acid; D017430:Prostate-Specific Antigen