Topical combination of diclofenac, calcipotriol, and difluoromethylornithine has beneficial effects comparable to 5-fluorouracil for the treatment of non-melanoma skin cancer in mice

References

• Guy GP, Ekwueme DU. Years of potential life lost and indirect costs of melanoma and non-melanoma skin cancer: a systematic review of the literature. Pharmacoeconomics. 2011;29:863–74.
   PubMed Web of Science ®Google Scholar
• Rogers HW, Weinstock MA, Harris AR, Hinckley MR, Feldman SR, Fleischer AB, et al.. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146:283–7.
   PubMed Web of Science ®Google Scholar
• Trakatelli M, Ulrich C, del Marmol V, Euvrard S, Euvard S, Stockfleth E, et al.. Epidemiology of nonmelanoma skin cancer (NMSC) in Europe: accurate and comparable data are needed for effective public health monitoring and interventions. Br J Dermatol. 2007;156 (Suppl):1–7.
   PubMed Web of Science ®Google Scholar
• Roewert-Huber J, Stockfleth E, Kerl H. Pathology and pathobiology of actinic (solar) keratosis – an update. Br J Dermatol. 2007;157(Suppl 2):18–20.
   PubMed Web of Science ®Google Scholar
• Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B Biol. 2001;63:8–18.
   PubMed Web of Science ®Google Scholar
• McGillis ST, Fein H. Topical treatment strategies for non-melanoma skin cancer and precursor lesions. Semin Cutan Med Surg. 2004;23:174–83.
   PubMed Web of Science ®Google Scholar
• Lu YP, Lou YR, Xie JG, Yen P, Huang MT, Conney AH. Inhibitory effect of black tea on the growth of established skin tumors in mice: effects on tumor size, apoptosis, mitosis and bromodeoxyuridine incorporation into DNA. Carcinogenesis. 1997;18:2163–9.
   PubMed Web of Science ®Google Scholar
• Chilampalli C, Guillermo R, Zhang X, Kaushik RS, Young A, Zeman D, et al.. Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action. BMC Cancer. 2011;11:456.
   PubMed Web of Science ®Google Scholar
• Lu Y-P, Lou Y-R, Xie J-G, Peng Q-Y, Liao J, Yang CS, et al.. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc Natl Acad Sci USA. 2002;99:12455–60.
   PubMed Web of Science ®Google Scholar
• Lerche CM, Philipsen PA, Poulsen T, Wulf HC. High death rate in mice treated topically with diclofenac. Exp Dermatol. 2011;20:336–8.
   PubMed Web of Science ®Google Scholar
• Pommergaard HC, Burcharth J, Rosenberg J, Raskov H. Topical treatment with diclofenac, calcipotriol (vitamin-D3 analog) and difluoromethylornithine (DFMO) does not prevent non-melanoma skin cancer in mice. Cancer Invest. 2013;31:92–6.
   PubMed Web of Science ®Google Scholar
• Bowden GT. Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling. Nat Rev Cancer. 2004;4:23–35.
   PubMed Web of Science ®Google Scholar
• Grewe M, Trefzer U, Ballhorn A, Gyufko K, Henninger H, Krutmann J. Analysis of the mechanism of ultraviolet (UV) B radiation-induced prostaglandin E2 synthesis by human epidermoid carcinoma cells. J Invest Dermatol. 1993;101:528–31.
   PubMed Web of Science ®Google Scholar
• Pentland AP, Schoggins JW, Scott GA, Khan KN, Han R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis. 1999;20:1939–44.
   PubMed Web of Science ®Google Scholar
• An KP, Athar M, Tang X, Katiyar SK, Russo J, Beech J, et al.. Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches. Photochem Photobiol. 2002;76:73–80.
   PubMed Web of Science ®Google Scholar
• Tiano HF, Loftin CD, Akunda J, Lee CA, Spalding J, Sessoms A, et al.. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res. 2002;62:3395–401.
   PubMed Web of Science ®Google Scholar
• Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7:684–700.
   PubMed Web of Science ®Google Scholar
• Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, et al.. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252–61.
   PubMed Web of Science ®Google Scholar
• Gilmour SK. Polyamines and nonmelanoma skin cancer. Toxicol Appl Pharmacol. 2007;224:249–56.
   PubMed Web of Science ®Google Scholar
• Fischer SM, Lee M, Lubet RA. Difluoromethylornithine is effective as both a preventive and therapeutic agent against the development of UV carcinogenesis in SKH hairless mice. Carcinogenesis. 2001;22:83–8.
   PubMed Web of Science ®Google Scholar
• Gensler HL. Prevention by alpha-difluoromethylornithine of skin carcinogenesis and immunosuppression induced by ultraviolet irradiation. J Cancer Res Clin Oncol. 1991;117:345–50.
   PubMed Web of Science ®Google Scholar
• Rebel H, van Steeg H, Beems RB, Schouten R, de Gruijl FR, Terleth C. Suppression of UV carcinogenesis by difluoromethylornithine in nucleotide excision repair-deficient Xpa knockout mice. Cancer Res. 2002;62:1338–42.
   PubMed Web of Science ®Google Scholar
• Dillaha CJ, Jansen GT, Honeycutt WM, Bradford AC. Selective cytotoxic effect of topical 5-fluorouracil. Arch Dermatol. 1983;119:774–83.
   PubMedGoogle Scholar
• Mohs FE, Jones DL, Bloom RF. Tendency of fluorouracil to conceal deep foci of invasive basal cell carcinoma. Arch Dermatol. 1978;114:1021–2.
   PubMedGoogle Scholar
• Gupta AK, Davey V, McPhail H. Evaluation of the effectiveness of imiquimod and 5-fluorouracil for the treatment of actinic keratosis: Critical review and meta-analysis of efficacy studies. J Cutan Med Surg. 2005;9:209–14.
   PubMed Web of Science ®Google Scholar
• Geisse JK, Rich P, Pandya A, Gross K, Andres K, Ginkel A, et al.. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol. 2002;47:390–8.
   PubMed Web of Science ®Google Scholar
• Huber A, Huber JD, Skinner RB Jr, Kuwahara RT, Haque R, Amonette RA. Topical imiquimod treatment for nodular basal cell carcinomas: an open-label series. Dermatol Surg. 2004;30:429–30.
   PubMed Web of Science ®Google Scholar
• Shumack S, Robinson J, Kossard S, Golitz L, Greenway H, Schroeter A, et al.. Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma: comparison of dosing regimens. Arch Dermatol. 2002;138:1165–71.
   PubMed Web of Science ®Google Scholar
• Calzavara-Pinton PG. Repetitive photodynamic therapy with topical delta-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours. J Photochem Photobiol B. 1995;29:53–7.
   PubMed Web of Science ®Google Scholar
• Fink-Puches R, Hofer A, Smolle J, Kerl H, Wolf P. Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light. J Photochem Photobiol B. 1997;41:145–51.
   PubMed Web of Science ®Google Scholar
• Jeffes EW, McCullough JL, Weinstein GD, Fergin PE, Nelson JS, Shull TF, et al.. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study. Arch Dermatol. 1997;133:727–32.
   PubMed Web of Science ®Google Scholar
• Jeffes EW, McCullough JL, Weinstein GD, Kaplan R, Glazer SD, Taylor JR. Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. J Am Acad Dermatol. 2001;45:96–104.
   PubMed Web of Science ®Google Scholar
• Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B. 1990;6:143–8.
   PubMed Web of Science ®Google Scholar
• Cairnduff F, Stringer MR, Hudson EJ, Ash DV, Brown SB. Superficial photodynamic therapy with topical 5-aminolaevulinic acid for superficial primary and secondary skin cancer. Br J Cancer. 1994;69:605–8.
   PubMed Web of Science ®Google Scholar
• Soler AM, Angell-Petersen E, Warloe T, Tausjo J, Steen HB, Moan J, et al.. Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Photochem Photobiol. 2000;71:724–9.
   PubMed Web of Science ®Google Scholar
• Wennberg AM, Lindholm LE, Alpsten M, Larko O. Treatment of superficial basal cell carcinomas using topically applied delta-aminolaevulinic acid and a filtered xenon lamp. Arch Dermatol Res. 1996;288:561–4.
   PubMed Web of Science ®Google Scholar
• Elmets CA, Viner JL, Pentland AP, Cantrell W, Lin H-Y, Bailey H, et al.. Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2010;102:1835–44.
   PubMed Web of Science ®Google Scholar
• Alberts DS, Dorr RT, Einspahr JG, Aickin M, Saboda K, Xu MJ, et al.. Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine. Cancer Epidemiol Biomarkers Prev. 2000;9:1281–6.
   PubMed Web of Science ®Google Scholar
• Bailey HH, Kim K, Verma AK, Sielaff K, Larson PO, Snow S, et al.. A randomized, double-blind, placebo-controlled phase 3 skin cancer prevention study of {alpha}-difluoromethylornithine in subjects with previous history of skin cancer. Cancer Prev Res. 2010;3:35–47.
   PubMed Web of Science ®Google Scholar
• Tang JY, Parimi N, Wu A, Boscardin WJ, Shikany JM, Chren M-M, et al.. Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Cancer Causes Control. 2010;21:387–91.
   PubMed Web of Science ®Google Scholar
• Gandini S, Raimondi S, Gnagnarella P, Doré J-F, Maisonneuve P, Testori A. Vitamin D and skin cancer: a meta-analysis. Eur J Cancer. 2009;45:634–41.
   PubMed Web of Science ®Google Scholar
• Dajani EZ, Islam K. Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man. J Physiol Pharmacol. 2008;59(Suppl 2):117–33.
   PubMedGoogle Scholar
• Lanas A, Sopeña F. Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications. Gastroenterol Clin North Am. 2009;38:333–52.
   PubMed Web of Science ®Google Scholar
• Carbone PP, Pirsch JD, Thomas JP, Douglas JA, Verma AK, Larson PO, et al.. Phase I chemoprevention study of difluoromethylornithine in subjects with organ transplants. Cancer Epidemiol Biomarkers Prev. 2001;10:657–61.
   PubMed Web of Science ®Google Scholar