Phytotherapy in Biochemically Recurrent Prostate Cancer

A pilot study

By Michael Traub, ND, DHANP, FABNO

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This paper is part of NMJ's 2017 Oncology Special Issue. Read the paper or download the full issue here.

Reference

Van Die MD, Williams SG, Emery J, et al. A placebo-controlled double-blinded randomized pilot study of combination phytotherapy in biochemically recurrent prostate cancer. Prostate. 2017;77(7):765-775.

Design

Double-blind, randomized, placebo-controlled 2-cohort parallel trial; participants were assessed at baseline and at week 12.

Participants

Twenty-two Australian men aged 56 to 84 years with biochemically recurrent prostate cancer (BCR) recruited from a cancer hospital in Melbourne, Australia.

Study Medication and Dosage

Participants randomly allocated to the experimental group took 2 capsules of broccoli sprout concentrate 20:1 twice a day (each equivalent to fresh sprouts 2,000 mg [8 g/day]), and 2 capsules containing 30 mg resveratrol (from Polygonum cuspidatum extract 100:1) and 100 mg catechins (from green tea leaf extract 25:1) per capsule, twice a day. The placebo group took 2 capsules containing microcrystalline cellulose, calcium hydrogen phosphate, magnesium stearate, and hypromellose twice a day and two 100-mg capsules of powdered green oats twice a day.

Outcome Measures

To estimate PSA doubling time, 3 to 6 prostate specific antigen (PSA) measurements were obtained at least 12 months before enrollment. Clinical measures collected at baseline were PSA, blood urea nitrogen (BUN), electrolytes, liver function tests, estradiol, blood pressure, BMI, and Karnofsky performance score. Quality of life was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLA-C30) and Prostate 25 (EORTC PR-25), administered at baseline and week 12, and the International Prostate Symptom Score (IPSS) and Hospital Anxiety and Depression Scale (HADS). Dietary intake of trial substances was recorded in weekly diaries, along with adverse events.

Key Findings

The study was not adequately powered to detect effects of the phytotherapeutic intervention on PSA doubling times from baseline to 12 weeks. There were no statistically significant differences in prostate symptoms as measured on the IPSS, anxiety and depression as measured on the HADS, or in the EORTC QLA-C30 or EORTC PR-25. The phytotherapeutic combination was well-tolerated. Few and mild side effects were reported, and adherence to protocol was high.

The width of the confidence intervals of PSA doubling times by group allowed for the possibility that the herbal group would have a better PSA outcome in a future adequately powered trial, consistent with other recent promising trials of similar herbal interventions.1-3

Practice Implications

Thirty percent of patients treated for prostate cancer with prostatectomy or radiation therapy—and more than 50% in high-risk cases—eventually develop potentially life-threatening recurrences,4 which are often detected when their PSA levels start rising during post-treatment surveillance. The standard treatment for recurrent prostate cancer, whether biochemical or metastatic, is intermittent or continuous androgen deprivation therapy (ADT). Once the disease is “castration resistant,” ADT is typically continued for life.

There is a pressing need for new, minimally toxic therapies for prostate cancer.

Androgens and androgen deprivation have profound effects on the immune system, a finding that has become more appreciated in an era where exploration of immune-based treatments for cancer continues to advance. Preclinical studies suggest that androgen deprivation could potentially positively or negatively affect the use of approved or investigative immunotherapies for the treatment of prostate cancer. Initially, ADT is highly effective in suppressing prostate cancer; however, the side effects are potentially significant and include fatigue; weight gain; muscle loss; hot flashes; erectile dysfunction; loss of libido; loss of strength, muscle mass, and bone density; cognitive impairment; depression; osteoporotic fractures; anemia; and increased risk of diabetes, metastatic disease, and cardiovascular events.5-7

In the context of an otherwise asymptomatic individual, such effects are especially concerning, because treatment is applied frequently for many years. Furthermore, ADT is not curative.8 Most tumors progress to metastatic castration-resistant prostate cancer after ADT in a mean interval of 38 months,4 are recalcitrant to current therapy, and progress rapidly. There is a pressing need for new, minimally toxic therapies for prostate cancer.

Despite some initial encouragement from cohort and small prospective studies, lycopene, saw palmetto, or genistein extracts evaluated within more scientifically robust analyses did not demonstrate a benefit for prostate cancer.9 On the other hand, preliminary clinical trials have shown benefit from sulforaphane, broccoli, green tea, turmeric, pomegranate juice and extract, and white button mushroom.10-15 Although the Australian study in this review was not sufficiently powered to demonstrate efficacy, it does demonstrate the feasibility of a randomized trial of a combination of sulforaphane, green tea, turmeric, and resveratrol for treatment of men with prostate cancer, strengthening the foundation for future investigations. Moreover, the latter 2 polyphenols have shown synergism in a preclinical bioavailability study, which supports their use in combination.16 This reviewer is currently seeking approval and funding for a clinical trial of white button mushroom in prostate cancer treatment.

The main limitation of this Australian study was the slow rate of recruitment. The authors point out that accrual of participants was limited by the advent of Prostate-Specific Membrane Antigen (PSMA) PET scans at the recruitment hospital, which allowed for detection of micro-metastases in many otherwise eligible patients with BCR, who were then offered salvage treatments. A major advance in detecting metastatic prostate cancer, PSMA PET imaging uses a radioactive peptide, Gallium-68, to mark an antigen receptor (PSMA) that sits on the surface of every prostate cancer cell, providing valuable information to help physicians make more informed treatment decisions, as well as aiding in recruitment and monitoring of research subjects.

About the Author

Michael Traub, ND, DHANP, FABNO, completed pre-med studies at the University of California at Irvine. He graduated from National University of Naturopathic Medicine in 1981 and completed a residency there in Family Practice and Homeopathy. In 2006, Traub was honored with the American Association of Naturopathic Physicians (AANP) Physician of the Year Award in recognition for his many years of service, which included serving as AANP president from 2001 to 2003. His father was a dermatologist, and this inspired Traub to undertake extra study in this subject and become the leading expert in dermatology in the naturopathic profession. He has taught dermatology at 5 of the 7 accredited naturopathic medical schools in North America and is the author of Essentials of Dermatologic Diagnosis and Integrative Therapeutics. A fellow of the American Board of Naturopathic Oncology, Traub has been actively engaged in clinical research throughout most of his career and is currently a co-investigator in the Canadian/US Integrative Oncology Study. His most recent major publication, “Impact of Vitamin D3 Dietary Supplement Matrix on Clinical Response,” appears in a 2014 issue of the Journal of Clinical Endocrinology and Metabolism. Traub has served as medical director of Lokahi Health Center in Kailua Kona, Hawaii for the past 31 years.

References

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  2. Thomas R, Williams M, Sharma H, et al. A double-blind, placebo-controlled randomized trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the UK NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014;17(2):180-186.
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  11. Thomas R, Williams M, Sharma H, et al. A double-blind, placebo-controlled randomized trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the UK NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014;17(2):180-186.
  12. Dorff, TB, Grosen S, Tsao-Wei DD, et al. A phase II trial of a combination herbal supplement for men with biochemically recurrent prostate cancer. Prostate Cancer Prostatic Dis. 2014;17(4):359-365.
  13. Paller CJ, Ye X, Wozniak PJ, et al. A randomised phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013;16(1):50-55.
  14. McLarty J, Bigelow RLH, Smith M, Elmajian D, Ankem M, Cardelli JA. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res. 2009;2(7):673-682.
  15. van Die MD, Bone KM, Emery J, Williams SG, Pirotta MV, Paller CJ. Phytotherapeutic interventions in the management of biochemically recurrent prostate cancer: a systematic review of randomised trials. BJU Int. 2016;117(Suppl 4):17-34.
  16. Lund KC, Pantuso T. Combination effects of quercetin, resveratrol and curcumin on in vitro intestinal absorption. J Rest Med. 2014;3(1):112-120.