Phase II Study of Pomegranate Juice for Men with Rising Prostate-Specific Antigen following Surgery or Radiation for Prostate Cancer

Abstract

Purpose: 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. Experimental Design: 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 V7. 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.Adenocarcinoma of the prostate is currently the most common malignancy in men in the United States comprising 29% of all cancers. This year an estimated 232,090 men will be newly diagnosed with prostate cancer (1). There has been a trend toward improved survival in prostate cancer over the past several years. Prostate cancer 5-year survival rates have increased from 67% for the period of 1974 to 1976 to 92% for the period of 1989 to 1995 (2). However, prostate cancer remains the second most common cause of cancer death in men in the United States, accounting for 11% of all cancer deaths. This year an estimated 30,350 men will die of prostate cancer (1).Primary management of prostate cancer for the majority of patients consists of either radical surgery or radiation therapy. Although this is adequate for permanent disease control in many patients, a significant number of patients relapse and ultimately develop metastatic disease. Radical prostatectomy is currently the most commonly used therapy for curative intent (3). However, approximately one third of prostate cancer patients with clinically confine...

Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells

“…The potent anti-proliferative activities of the non-edible pomegranate extracts have been attributed to the high amount of phenolics present in the extracts [30,31]. Literature abounds in examples of the anti-proliferative and anticancer effect of pomegranate fruit and juice, all of which have been attributed to the high level of phenolic compounds present [13,16,20,23,[32][33][34][35][36][37][38]. Among the different mechanisms of action involved, plant phenolics exert chemopreventive activity via its antioxidative potential [7].…”

“…Pomegranate-derived ellagitannins showed in vitro anti-proliferative and anti-aromatase activity in breast cancer cells [13], while pomegranate juice consumption revealed a significant prolongation of prostatespecific antigen doubling time, in both an initial phase II clinical trial in patient with prostate cancer [20] and a randomized phase II study [21]. Raw pomegranate peel extract offers selective cytotoxic activity against promyelocytic (HL60) cell lines and immune-stimulatory effect in peripheral blood mononuclear cells [22].…”

Dietary Supplement Use in Cancer Care: Help or Harm

“…Total prostate specific antigen (PSA) did not change, and men with symptomatic benign prostatic hyperplasia reported symptom reduction. Pomegranate juice (8 oz of concentrate, POM Wonderful variety), when given to men with a rising PSA following surgery or radiation, increased the mean PSA-doubling time from 15 months to 54 months (P < .001) without reports of adverse events [197]. When given a dietary supplement containing soy, lycopene, silymarin, and antioxidants (formulary details not given) following surgery or radiation for 10 weeks, 49 men showed an increase of PSAdoubling time from 445 days to 1,150 days, along with significant decreases in PSA slope (P ¼ .03) [198].…”

“…Increased PSA-doubling time [197] Soy in complex formula in prostate cancer patients with rising PSA after radiation or surgery…”

Pomegranate (Punica granatum): a natural source for the development of therapeutic compositions of food supplements with anticancer activities based on electron acceptor molecular characteristics

“…For example, pomegranate has been found to possess well-documented cancer chemopreventive and chemotherapeutic effects against prostate cancer [10][11][12][13]. The results of a Phase II clinical study of patients with rising prostate-specific antigen (PSA) levels following surgery or radiation for prostate cancer demonstrated that pomegranate juice produced statistically significant prolongation of PSA doubling times, suggesting that pomegranate consumption may retard prostate cancer progression [14].Despite numerous published results of in silico, in vitro and in vivo studies of pomegranate, several questions remain, including which components of this dietary agent are responsible for these anti-cancer activities and by what mechanism do they actually suppress cancers. Analysis of the electronic properties of 101 pomegranate ingredients revealed that nearly 50% of these compounds represent potentially carcinostatic substances with strong electron-acceptor properties.…”