Fax: (520) 626-6033
Randomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma†
Evaluation of potential chemopreventive activity
Article first published online: 17 MAY 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 23, pages 5848–5856, 1 December 2012
How to Cite
Curiel-Lewandrowski, C., Swetter, S. M., Einspahr, J. G., Hsu, C.-H., Nagle, R., Sagerman, P., Tangrea, J., Parnes, H., Alberts, D. S. and Chow, H.-H. (2012), Randomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma. Cancer, 118: 5848–5856. doi: 10.1002/cncr.27540
The authors acknowledge Chris Brooks; Nancy DiSanto RN, BSN; Donna Vining, RN; Steve Rodney, BS; Laura Duckett; Wade Chew; and Mary Krutzsch, BS, for their invaluable assistance in the performance of the clinical study and endpoint assays. This manuscript is dedicated to the memory of Nancy DiSanto, RN, for her invaluable contribution and dedication to the study while battling the hardships of cancer.
- Issue published online: 19 NOV 2012
- Article first published online: 17 MAY 2012
- Manuscript Accepted: 30 JAN 2012
- Manuscript Revised: 29 JAN 2012
- Manuscript Received: 20 NOV 2011
- prevention and control;
- anti-inflammatory agents;
- atypical nevi
Reduced melanoma risk has been reported with regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions such as atypical nevi has not been evaluated.
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 ≥4 mm in size and 1 benign nevus (BN) were randomized to sulindac (150 mg twice a day) or placebo for 8 weeks. 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 ± 2.24 μg/mL in plasma, and 0.51 ± 1.05, 1.38 ± 2.86, and 0.12 ± 0.12 μg/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.
Eight weeks of sulindac intervention resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite, in BN but did not effectively modulate VEGFA and cleaved caspase-3 expression. Study limitations included limited exposure time to sulindac and the need to optimize a panel of biomarkers for NSAID intervention studies. Cancer 2012. © 2012 American Cancer Society.