A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia

Abstract

A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27). Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and posttreatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Fifty-eight men completed the trial. Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1, or IGF binding protein 3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy, or inflammation posttreatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated.

Trial registration: ClinicalTrials.gov identifier: NCT00416325.

ACKNOWLEDGMENTS

The authors wish to express appreciation to Michael Schlicht, Peter Nguyen, Galina Khramtsova, Rachel Poon, Zohar Nir, Linlin Dong, Sheano Gold, Lindsay Gallagher, Roohalah Sharifi and Kevin McVary for their contributions to this project.

FUNDING

The study was funded by the National Institutes of Health/National Cancer Institute through RO1 CA90759 (PI: P. Gann). The funding agency had no role in the design or conduct of the study, or the preparation of the manuscript. Trial Registration: ClinicalTrials.gov Identifier NCT00416325