A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer

Abstract

Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease. Human intervention studies with cruciferous vegetable-rich diets also demonstrate modulation of gene expression in important pathways in prostate cells. Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on multiple tumor models. Our own work demonstrates that sulforaphane inhibits AR signaling in prostate cancer cells. Here, we report results from the first clinical trial of sulforaphane-rich extracts in men with prostate cancer. We treated 20 patients who had recurrent prostate cancer with 200μmoles/day of sulforaphane-rich extracts for a maximum period of 20 weeks and determined the proportion of patients with ≥50% PSA declines, the primary endpoint. Only one subject experienced a ≥50% PSA decline. Thus, the primary endpoint was not achieved. Seven patients experienced smaller PSA declines (<50%). There was also a significant lengthening of the on-treatment PSA doubling time (PSADT) compared with the pre-treatment PSADT [6.1 months pre-treatment vs. 9.6 months on-treatment (p=0.044)]. Finally, treatment with sulforaphane-rich extracts was safe with no Grade 3 adverse events. Treatment with 200μmoles/day of sulforaphane-rich extracts did not lead to ≥50% PSA declines in the majority of patients. However, because of the safety of treatment and the effects on PSADT modulation, further studies, including those with higher doses, may be warranted to clarify the role of sulforaphane as a prevention agent or treatment agent.

Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges

“…The fundamental role of epigenetic mechanisms in the regulation of gene expression and epigenetic aberrations implicated in various pathologies itself underlines the importance of compounds targeting them. It is much more challenging than it seems to develop dietary phytochemicals as effective chemopreventive and/or chemotherapeutic agents despite their widespread recognition and acceptance as evident from a large number of research publications [204–258]. There is still insufficient preclinical and clinical data published on the epigenetic changes induced by some of the dietary polyphenols, which remains a challenge and limitation, of the current data to acquire better insight on the molecular mechanisms responsible for these effects.…”

Food-based natural products for cancer management: Is the whole greater than the sum of the parts?

“…However, the intervention increased PSADT by 86% and mean changes in PSA after 6 months was significantly lower in the treatment group [88]. Further, consumption of 200 μmoles/day sulforaphane-rich broccoli sprout extract for 20 weeks by PCA patients with biochemical recurrence led to a < 50% decline in PSA in 7 out of 20 patients and increased PSADT with one patient showing ≥ 50% decline in PSA [89]. Additionally, consumption of 400 g broccoli by HGPIN patients for a year caused significant changes in androgen, TGF-β, IGF and EGF signaling and the mechanism suggested was a covalent interaction of sulforaphane with insulin, TGF-β and EGF peptides to form thiourea [90].…”

Broccoli-Derived Sulforaphane and Chemoprevention of Prostate Cancer: From Bench to Bedside

“…These clinical trials are currently in the early phases and have established safety and feasibility of oral administration of broccoli-derived constituents over long periods (up to 1 year) in a wide variety of settings ranging from pre-cancerous prostate conditions (high-grade PIN) to metastatic prostate cancer [54–56]. Two trials recently reported the role of SFN in biochemical [prostate specific antigen (PSA)] recurrence in patients with prostate cancer after definitive surgery or radiation therapy.…”

“…These trials are summarized below. In a single arm pilot study, Alumkal et al treated patients with biochemical recurrence of prostate cancer with 200 μmol of SFN for up to 20 weeks [56]. Eighteen of the twenty patients enrolled completed the pre-planned 20 weeks of treatment.…”

“…Seven patients had a decline in PSA with one patient having a decline by >50%. PSA doubling time improved from 6.1 months pre-study to 9.6 months on-study [56]. In another double-blind, multicenter trial from France, 81 prostate cancer patients with biochemical recurrence was randomized to receive 60 mg SFN or placebo for six months.…”