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This paper is part ofNMJ's Oncology Special Edition 2017. Read the newspaper or download the full edition here.
Relation
Van Die MD, Williams SG, Emery J, et al. A placebo-controlled, double-blind, randomized pilot study of combination phytotherapy for biochemically recurrent prostate cancer.prostate. 2017;77(7):765-775.
Draft
Double-blind, randomized, placebo-controlled 2-cohort parallel study; Participants were assessed at baseline and week 12.
Participant
Twenty-two Australian men aged 56 to 84 years with biochemically recurrent prostate cancer (BCR) were recruited from a cancer hospital in Melbourne, Australia.
Study medication and dosage
The participants randomly assigned to the experimental group took 2 capsules of broccoli sprout concentrate twice daily in a ratio of 20:1 (each equivalent to fresh sprouts 2,000 mg [8 g/day]) and 2 capsules with 30 mg resveratrol (fromPolygonum cuspidatumextract 100:1) and 100 mg catechins (from green tea leaf extract 25:1) per capsule, twice daily. The placebo group took 2 capsules of microcrystalline cellulose, calcium hydrogen phosphate, magnesium stearate and hypromellose twice daily and two 100 mg capsules of green oat powder twice daily.
Target parameters
To estimate the PSA doubling time, 3 to 6 prostate-specific antigen (PSA) measurements were performed at least 12 months before enrollment. Clinical measurements collected at baseline included PSA, blood urea nitrogen (BUN), electrolytes, liver function tests, estradiol, blood pressure, BMI, and Karnofsky performance score. Quality of life was measured with 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 the experimental substances was recorded along with adverse events in weekly diaries.
Key insights
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 by the IPSS, anxiety and depression as measured by 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 the protocol was high.
The width of the confidence intervals of PSA doubling times per group raised the possibility that the herbal group would achieve a better PSA result in a future adequately powered study, consistent with other recent promising studies 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,4which are often detected when their PSA levels begin to rise during post-treatment monitoring. 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 an urgent need for new, minimally toxic therapies for prostate cancer.
Androgens and androgen deprivation have profound effects on the immune system, a finding that is increasingly appreciated at a time when research into immune-based cancer treatments continues to advance. Preclinical studies suggest that androgen deprivation could potentially positively or negatively influence the use of approved or investigational immunotherapies for the treatment of prostate cancer. Initially, ADT is highly effective in suppressing prostate cancer; However, side effects are potentially significant and include fatigue; weight gain; muscle wasting; 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, metastases and cardiovascular events.5-7
In the context of an otherwise asymptomatic individual, such effects are particularly concerning because treatment is often used for many years. Furthermore, ADT is not curative.8Most tumors progress to metastatic castration-resistant prostate cancer after ADT at a median interval of 38 months.4are refractory to current therapy and progress rapidly. There is an urgent 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 in more scientifically based analyzes showed no benefit for prostate cancer.9On the other hand, preliminary clinical studies have shown the benefits of sulforaphane, broccoli, green tea, turmeric, pomegranate juice and extract, and white button mushrooms.10-15Although the Australian study in this review was not sufficiently powered to demonstrate effectiveness, it does demonstrate the feasibility of a randomized trial of a combination of sulforaphane, green tea, turmeric and resveratrol for the treatment of men with prostate cancer, thereby strengthening the basis for future research. Furthermore, the latter two polyphenols have shown synergism in a preclinical bioavailability study, supporting their use in combination.16This reviewer is currently seeking approval and funding for a clinical trial of white button mushrooms for the treatment of prostate cancer.
The main limitation of this Australian study was the slow recruitment rate. The authors note that the number of participants was limited by the advent of prostate-specific membrane antigen (PSMA) PET scans in the recruiting hospital, which allowed detection of micrometastases in many otherwise eligible patients with BCR who were then offered salvage treatments. A major advance in the detection of metastatic prostate cancer, PSMA-PET imaging uses a radioactive peptide, gallium-68, to label an antigen receptor (PSMA) located on the surface of each prostate cancer cell, providing valuable information to help physicians make more informed treatment decisions as well as assist in recruitment and monitoring Research topics.