Pilot evaluation of sulforaphane in melanoma patients with multiple atypical nevi: Tissue STAT1 and STAT3 as risk markers.

Abstract

TPS8606 Background: Increasing incidence and the poor prognosis of advanced melanoma argue for prevention efforts. Primary prevention and ultraviolet radiation (UVR) reduction have failed to gain traction in the population, making chemoprevention increasingly attractive. Sulforaphanes (SFN) are bioactive cruciferous compounds rich in the Brassica family, especially broccoli sprouts. Topical broccoli sprout extracts (BSE) decrease UVR erythema response in human skin, and may protect against UVR DNA damage. We have shown SFN inhibition of STAT3, which is constitutively activated in melanoma. We have therefore initiated a pilot study to evaluate BSE SFN in relation to melanoma progression biomarkers, and expression of STAT proteins of atypical melanocytic nevi. Methods: Melanoma patients with >2 atypical nevi are eligible for this trial, which aims to define the safety and clinico-pathological response to oral BSE-SFN. Secondary objectives are documentation of pharmacokinetics and pharmacodynamics of BSE-SFN, and the modulation of STAT 1/3 expression in atypical nevi and normal skin. Baseline photo-documentation and atypical nevus biopsy is performed to assess histopathological atypia and STAT 1/3 expression. Adjacent normal skin biopsies will establish baseline skin SFN levels. Six subjects per group will be accrued at daily dosages of 50, 100, and 200 μM. Subjects must abstain from dietary glucosinolates and isothiocyanates for the study duration and maintain food diaries. Following 27 days of BSE-SFN, blood samples, photography of index atypical nevi, and biopsies of selected atypical nevi and normal skin will be obtained. The three dosage groups will be analyzed for changes in atypia, SFN localization histopathology, and STAT 1/3 expression in the nevi and skin harvested at baseline and at study completion. This trial, UPCI 10-114, has received an IND and is IRB-approved. Accrual is planned to be completed during 2012-13.