Randomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma Full Text
Curiel–Lewandrowski C et al. – Eight weeks of sulindac intervention resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite, in benign nevus (BN) but did not effectively modulate vascular endothelial growth factor A (VEGFA) and cleaved caspase–3 expression. Study limitations included limited exposure time to sulindac and the need to optimize a panel of biomarkers for nonsteroidal anti–inflammatory drugs (NSAIDs) intervention studies.Methods
- This randomized, double-blind, placebo-controlled trial of sulindac was conducted in individuals with atypical nevi (AN) to determine bioavailability of sulindac and metabolites in nevi and effect on apoptosis and vascular endothelial growth factor A (VEGFA) expression in AN.
- Fifty subjects with AN ≥4mm in size and 1 benign nevus (BN) were randomized to sulindac (150mg twice a day) or placebo for 8weeks.
- Two AN were randomized for baseline excision, and 2 AN and BN were excised after intervention.
- Postintervention sulindac, sulindac sulfone, and sulindac sulfide concentrations were 0.31±0.36, 1.56±1.35, and 2.25±2.24µg/mL in plasma, and 0.51±1.05, 1.38±2.86, and 0.12±0.12µg/g in BN, respectively.
- Sulindac intervention did not significantly change VEGFA expression but did increase expression of the apoptotic marker cleaved caspase-3 in AN (increase of 3±33 in sulindac vs decrease of 25±45 in the placebo arm, P=.0056), although significance was attenuated (P=.1103) after adjusting for baseline expression.