Results of a Randomized Clinical Trial of the Action of Several Doses of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy

Abstract

Purpose: The purpose of this Phase II randomized-controlled trial was to evaluate the safety and effect of administering several doses of lycopene to men with clinically localized prostate cancer, on intermediate endpoint biomarkers implicated in prostate carcinogenesis.Methods: Forty-fi ve eligible men with clinically localized prostate cancer were supplemented with 15, 30 or 45 mg of lycopene or no supplement from biopsy to prostatectomy. Compliance to study agent, toxicity, changes in plasma lycopene, serum steroid hormones, PSA and tissue Ki-67 were analyzed from baseline to completion of intervention.Results: Forty-two of forty-fi ve fi ve subjects completed the intervention for approximately 30 days from the time of biopsy until prostatectomy. Plasma lycopene increased from baseline to post treatment in all treatment groups with greatest increase observed in the 45 mg lycopene-supplemented arm compared to the control arm without producing any toxicity. Overall, subjects with prostate cancer had lower baseline levels of plasma lycopene similar to those observed in previous studies in men with prostate cancer. Serum free testosterone decreased with 30 mg lycopene supplementation and total estradiol increased signifi cantly with 30 mg and 45 mg supplementation from baseline to end of treatment, with no signifi cant increases in serum PSA or tissue Ki-67. These changes were not signifi cant compared to the control arm for this sample size and duration of intervention. Conclusions:Although antioxidant properties of lycopene have been hypothesized to be primarily responsible for its benefi cial effects, our study suggests that other mechanisms mediated by steroid hormones may also be involved.

Chemoprevention Trial Feasibility Using Botanicals in Exceptionally High Risk Populations for Lung Cancer

“…This increased availability has encouraged subjects to opt out of participation in randomized clinical trials, where they have a chance at being assigned to a placebo arm [9,22,23]. Subjects have been unwilling to be randomized to placebo-control arms of trials, especially if the trial involves immense burden to them such as compliance to agent and diet, frequent visits, completion of monitoring tools and most importantly if these studies include invasive procedures for biomarker evaluation such as biopsy, fine needle aspirations or bronchoscopy [21].…”

Recent progress on nutraceutical research in prostate cancer

“…The patients were supplemented with lycopene during the time of biopsy to prostatectomy. It was found that the plasma lycopene increased while the level of serum free testosterone decreased after lycopene administration [78], suggesting that lycopene could suppress PSA expression. Indeed, lycopene supplements did reduce the expression of PSA in localized PCa [79].…”

Prostate cancer chemoprevention in men of African descent: current state of the art and opportunities for future research

“…Select soy isoflavones (namely, geinstein and daidzein) have weak estrogenic properties [81] and thus have been reported to exert antiproliferative effects on PCa due to suppression of AR-signaling pathways [82–85]. Indeed, consumption of soy food appears to be associated with a 30% reduction in PCa risk in the epidemiological studies, which were primarily conducted in populations with diets traditionally high in soy [86].…”

“…Soy isoflavones are known to influence multiple cellular pathways leading to aforementioned anticancerous effects; the authors recommend the following comprehensive review for detailed description of action of soy isoflavones on PCa [89]. Because down regulating the AR-mediated proliferation is thought to be one of the main mechanisms by which soy isoflavones exert its PCa chemopreventive action [82–85], it appears biologically plausible that AAM would have a different (and better) response to the intervention using this compound. Although no published data are available on soy isoflavones effectiveness specifically in AAM, there is a currently active phase II clinical trial of Purified Isoflavones in PCa (NCT01036321, Kumar P.I.…”

“…Biological PCa protective mechanisms appear to be related either to the antioxidative and anti-inflammatory [100–101] or apoptosis-inducing properties, such as ability to induce G0/G1 cycle arrest, apoptosis and delayed in vivo growth in different PCa cell lines [102–104]. Other mechanisms mediated by steroid hormones may also be involved [105]. Because PCa in AAM may demonstrates decreased apoptosis, lycopene might be more potent in men of African descent.…”