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 200 μmoles/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 200 μmoles/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.
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The authors thank Jed Fahey, Sc.D (Johns Hopkins University) and Paul Talalay, MD (Johns Hopkins University) for providing and preparing the extracts, Emily Ho, PhD (Oregon State University) for providing the internal sulforaphane standard, Evan Yu, MD (University of Washington) for referring numerous patients for this trial, and all the patients who volunteered to take part in this study. Infrastructure support for conduct of the trial was provided by a Prostate Cancer Clinical Trials Consortium Award (W81XWH-09-1-0140).
Conflicts of Interest
None to disclose
This clinical study was supported by a Kuni Foundation Clinical Trial Award (No#) (JA); a Kuni Foundation Scholar Award (No#) (JA); a Prostate Cancer Foundation Young Investigator Award (No#) (JA); Oregon Clinical and Translational Research Institute (OCTRI), grant numbers (UL1TR000128, KL2TR000152) from the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Biostatical support was in part provided by the Biostatistics Shared Resource of the Knight Cancer Institute (P30 CA069533) (MM). Finally, we also thank Platt Electric, Bruce Burns, and The Burns Family Fund of the Oregon Community Foundation for their philanthropic support of this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Rachel Slottke and Jacob Schwartzman each contributed equally
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Alumkal, J.J., Slottke, R., Schwartzman, J. et al. A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Invest New Drugs 33, 480–489 (2015). https://doi.org/10.1007/s10637-014-0189-z
- Prostate cancer
- Biochemical recurrence