Pantuck et al, 2006. A phase II, open-label, single-arm clinical trial was conducted at the Clark Urologic Center, David Geffen School of Medicine, University of California at Los Angeles.14 Forty-six men (ages are not given) with recurrent prostate cancer and rising prostate-specific antigen (PSA) after surgery or radiotherapy were recruited for the study. Eligible patients had a detectable PSA > 0.2 and < 5 ng/ml that was documented as rising pretreatment PSA time points enough to calculate a baseline PSA doubling time (PSADT): no hormonal therapy before entering the study, no evidence of metastatic disease, and Gleason score ≤ 7. Of the patients enrolled, 68% were originally treated by radical prostatectomy, 10% by external beam radiotherapy, 10% by brachytherapy, 7% by surgery and radiation, and 5% by cryotherapy. Patients were treated with 8 ounces per day of POM Wonderful PJ until disease progression end points.
Serial PSA measurement before study entry determined a baseline PSADT. Each patient had a minimum of 3 pretreatment PSA values measured over a minimum of 6 months before study entry. Patients were then treated with PJ until meeting disease progression end points. Patients were followed in 3-month intervals for serum PSA, and blood and urine were collected for laboratory studies. Clinical end points included safety, effect on serum PSA, effect on serum hormone levels (testosterone, estradiol, sex-hormone binding globulin, dehydroepiandrosterone, insulin-like growth factor, and androstenedione), and in vitro assays that measure the effect of patients’ serum on LNCaP cell (a prostate cancer cell line) growth and apoptosis as well as nitric oxide and lipid peroxidation. The primary end point was effect on PSA variables, such as change in PSADT.
Table 1. Nutrition Facts For Pom Wonderful®
Pomegranate Juice Based On 4 Lots Analyzed
Mean PSADT significantly increased with treatment from a mean of 15 months at baseline to 54 months post-treatment (p < 0.001). Seven subjects actually had negative PSADT slopes (their PSA decreased over time) and were not included in the analysis. This exclusion results in an underestimation of the true PSADT. In vitro assays comparing pretreatment and post-treatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (p = 0.048 and 0.0004, respectively). Also found was a 23% increase in serum nitric oxide (p = 0.0085) as well as significant reductions in oxidative state and sensitivity to oxidation of serum lipids after PJ consumption (p < 0.02). There were no significant differences in pretreatment and post-treatment hormone levels. There were no serious adverse events and the PJ was well tolerated.
This robust open label study demonstrates a clinically significant improvement in PSADT. As noted by the investigators of this study, the benefits noted are in assays that are not yet validated. Future clinical trials will be needed to demonstrate whether improvement in biomarkers (e.g., PSDAT) correlate with clinical benefit. A confirmatory phase III placebo-controlled clinical trial using POM Wonderful PJ began recruiting patients in April 2006 and hopes to address some of the limitations of the phase II study summarized above.