A Placebo-Controlled Double-Blinded Randomized Pilot Study of Combination Phytotherapy in Biochemically Recurrent Prostate Cancer.
BACKGROUND
Men with biochemical recurrence of prostate cancer following local therapies often use natural supplements in an attempt to delay metastases and/or avoid the need for more aggressive treatments with undesirable side-effects. While there is a growing body of research into phytotherapeutic agents in this cohort, with some promising results, as yet no definitive recommendations can be made. This pilot study was undertaken to assess the feasibility of a fully-powered study to examine the effects of this phytotherapeutic intervention (containing turmeric, resveratrol, green tea and broccoli sprouts) on PSA doubling time in men with biochemical recurrence with a moderate PSA rise rate.


METHODS
A double blind, randomized, placebo-controlled parallel trial was conducted with 22 men with biochemically recurrent prostate cancer and a moderate rise rate (PSA doubling time of 4-15 months and no evidence of metastases from conventional imaging methods). Patients were randomized to either the active treatment arm or placebo for 12 weeks. The primary endpoints were feasibility of study recruitment and procedures, and measurement of proposed secondary endpoints (prostate symptoms, quality of life, anxiety, and depression as measured on the EORTC QLQ-C30 and PR-25, the IPSS and HADS). Data were collected to estimate PSA-log slopes and PSA-doubling times, using a mixed model, for both the pre-intervention and post-intervention periods.


RESULTS
Adherence to study protocol was excellent, and the phytotherapeutic intervention was well-tolerated, with similar numbers of mild-to-moderate adverse events in the active and placebo arms. Both the intervention and data collection methods were acceptable to participants. No statistical difference between groups on clinical outcomes was expected in this pilot study. There was between-subject variation in the PSA post treatment, but on average the active treatment group experienced a non-significant increase in the log-slope of PSA (pre-treatment doubling time = 10.2 months, post-treatment doubling time = 5.5 months), and the placebo group experienced no change in the log-slope of PSA (pre-treatment doubling time = 10.8 months, post-treatment doubling time = 10.9 months).


CONCLUSIONS
The findings suggest that a fully powered study of this combination is feasible in men with biochemically recurrent prostate cancer and a moderate PSA rise rate. Prostate 77:765-775, 2017. © 2017 Wiley Periodicals, Inc.
Department of General Practice, University of Melbourne, Parkville, Victoria, Australia.
M Diana
MD
van Die
Department of General Practice, University of Melbourne, Parkville, Victoria, Australia.|Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Scott G
SG
Williams
Department of General Practice, University of Melbourne, Parkville, Victoria, Australia.
Jon
J
Emery
Integria (MediHerb), Warwick, Queensland, Australia.|New York Chiropractic College, Seneca Falls, New York.
Kerry M
KM
Bone
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
Jeremy M G
JM
Taylor
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
Elizabeth
E
Lusk
Department of General Practice, University of Melbourne, Parkville, Victoria, Australia.
Marie V
MV
Pirotta
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D001526:Behavioral Symptoms / Q000175:diagnosis / Q000209:etiology; D014408:Biomarkers, Tumor / Q000097:blood; D001937:Brassica; D030024:Curcuma; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000523:psychology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000473:pathology / Q000523:psychology / Q000628:therapy; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000009:adverse effects; D063189:Symptom Assessment / Q000379:methods; D013662:Tea; D013997:Time Factors; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D013267:Stilbenes; D013662:Tea; D017430:Prostate-Specific Antigen; D000077185:Resveratrol
botanical medicine; early prostate cancer; herbal medicine; phytotherapy; randomized controlled trial