Background Actinic keratosis is the most prevalent premalignant skin disorder in the white population. Current guidelines provide no clear recommendations about preferred treatments. Methods The parameters; effectiveness, treatment duration, recurrence, side effects and cost of treatment were investigated for three frequently used topical therapies which were then compared with a most recent developed topical therapy. Published clinical data obtained from the literature was used to compare these parameters for 5-fluorouracil, imiquimod and diclofenac and relate them with the newly developed Curaderm. Results A wide variation in the concentrations of the active anti-keratotic ingredients, application frequency, duration of treatment, recurrence rates and cost of treatment exist between the different topical therapies. The efficacy rates and side effects were less variable. Overall, Curaderm is the most suitable treatment for actinic keratosis. Clinical evidence is presented illustrating the effects of Curaderm on field-directed treatments and solitary treatments of actinic keratoses. Conclusions Current medical guidelines do not provide clear recommendations on which treatment approach for actinic keratosis is preferred. Direct head-to-head comparison between treatments with emphasis on efficacy, safety, treatment duration, compliance, convenience, cosmetic outcome, patient acceptance and cost should be available to the patient, the practising physician, healthcare system and should assist in therapeutic treatment guidelines and policymaking. Given the very favourable profiles of these parameters with Curaderm when compared with other home-based treatments, it should be considered that Curaderm is first-in-line.
References
[1]
Smith, Y. (2023) Actinic Keratosis Epidemiology. News Medical. https://www.news-medical.net/health/Actinic-Keratosis-Epidemiology.aspx
[2]
Shreve, C., Shropshire, C. and Adler, J.R. (2020) Metastatic Squamous Cell Carcinoma: A Cautionary Tale. Cureus, 12, e10879. https://doi.org/10.7759/cureus.10879
[3]
Zhang, N., Yin, Y., Xu, S. and Chen, W. (2008) 5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies. Molecules, 13, 1551-1569. https://doi.org/10.3390/molecules13081551
[4]
Bubna, A.K. (2015) Imiquimod—Its Role in the Treatment of Cutaneous Malignancies. Indian Journal of Pharmacology, 47, 354-359. https://doi.org/10.4103/0253-7613.161249
[5]
Gan, T.J. (2010) Diclofenac: An Update on Its Mechanism of Action and Safety Profile. Current Medical Research and Opinion, 26, 1715-1731. https://doi.org/10.1185/03007995.2010.486301
[6]
An, W.X., Lai, H.L., Zang, Y.Y., Liu, M.H., Lin, X.K. and Cao, S.S. (2019) Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines. Frontiers in Pharmacology. 19, Article 758. https://doi.org/10.3389/fphar.2019.00758
[7]
Li, X., Zhao, Y., Wu, W.K., Liu, S., Cui, M. and Lou, H. (2011) Solamargine Induces Apoptosis with P53 Transcription-Dependent and Transcription-Independent Pathways in Human Osteosarcoma U2OS Cells. Life Sciences, 88, 314-321. https://doi.org/10.1016/j.lfs.2010.12.006
[8]
Al Sinani, S.S., Eltayeb, E.A., Coomber, B.L. and Adham, S.A. (2016) Solamargine Triggers Cellular Necrosis Selectively in Different Types of Human Melanoma Cancer Cells through Extrinsic Lysosomal Mitochondrial Death Pathways. Cancer Cell International, 16, Article No. 11. https://doi.org/10.1186/s12935-016-0287-4
[9]
Zang, X.H., Yan, Z.P., Xu, T.T., A, Z.T., Chen, W.Z., Wang, X.S., Huang, M.M. and Zu, F.S. (2018) SM Derived from Solanum Nigrum Induces Apoptosis of Human Cholangio Carcinoma QBC939 Cells. Oncology Letters, 15, 6329-6335. https://doi.org/10.3892/ol.2018.8171
[10]
Al Sinani, S.S. and Eltayeb, E.A. (2017) The Steroidal Glycoalkaloids Solamargine and Solasonine in Solanum Plants. South African Journal of Botany, 112, 253-269. https://doi.org/10.1016/j.sajb.2017.06.002
[11]
Kalalinia, F. and Korimi-Sani, I. (2017) Anticancer Properties of Solamargine: A Systematic Review. Phytotherapy Research, 31, 858-870. https://doi.org/10.1002/ptr.5809
[12]
Sani, I.K., Marashi, S.H. and Kalalinia, F. (2015) Solamargine Inhibits Migration and Invasion of Human Hepatocellular Carcinoma Cells through Down-Regulation of Matrix Metalloproteinases 2 and 9 Expression and Activity. Toxicology in Vitro, 29, 893-900. https://doi.org/10.1016/j.tiv.2015.03.012
[13]
Cham, B.E. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713. https://doi.org/10.4236/ijcm.2017.812064
[14]
Cham, B.E. (2013) Inspired by Nature, Proven by Science. The New Generation Cancer Treatment That Causes Cancer Cells to Commit Suicide. Colorite Graphics Printers, Port Vila.
[15]
Li, X., Zhao, Y., Liu, S.S., Cui, M. and Lou, H.X. (2011) Induction of Actin Disruption and Downregulation of P-Glycoprotein Expression of Solamargine in Multidrug-Resistant K562/A02 Cells. Chinese Medical Journal, 124, 2038-2044.
[16]
Cham, B.E. (2013) Solasodine Glycosides: A Topical Therapy for Actinic Keratosis. A Single-Blind, Randomized, Placebo-Controlled, Parallel Group Study with Curaderm. Journal of Cancer Therapy, 4, 588-596. https://doi.org/10.4236/jct.2013.42076
[17]
Cham, B.E. and Meares, H.M. (1987) Glycoalkaloids from Solanum sodomaeum Are Effective in the Treatment of Skin Cancers in Man. Cancer Letters, 36, 111-118. https://doi.org/10.1016/0304-3835(87)90081-4
[18]
Wu, Y.H., Tang, N., Cai, L.H. and Li, Q.L. (2019) Relative Efficacy of 5-Fluorouracil Compared with Other Treatments among Patients with Actinic Keratosis: A Network Meta-Analysis. Dermatologic Therapy, 32, e12822. https://doi.org/10.1111/dth.12822
[19]
Askew, D.A., Micka, S.M., Soyer, H.P. and Wilkinson, D. (2009) Effectiveness of 5-Fluorouracil Treatment of Actinic Keratosis—A Systematic Review of Randomized Control Trials. International Journal of Dermatology, 48, 453-463. https://doi.org/10.1111/j.1365-4632.2009.04045.x
[20]
Gupta, A.K., Davey, V. and Mcphail, H. (2005) Evaluation of the Effectiveness of Imiquimod and 5-Fluorouracil for the Treatment of Actinic Keratosis: Critical Review and Meta-Analysis of Efficacy Studies. Journal of Cutaneous Medicine and Surgery, 9, 209-214. https://doi.org/10.1177/120347540500900501
[21]
Steeb, T., Wessely, A., Petzold, A., Brinker, T.J., et al. (2021) Long Term Recurrence Rates of Actinic Keratosis: A Systematic Review and Pooled Analysis of Randomized Control Trials. Journal of the American Academy of Dermatology, 86, 1116-1119. https://doi.org/10.1016/j.jaad.2021.04.017
[22]
Hadley, G., Derry, S. and Moore, R.A. (2006) Imiquimod for Actinic Keratosis: Systematic Review and Meta-Analysis. Journal of Investigative Dermatology, 126, 1251-1255. https://doi.org/10.1038/sj.jid.5700264
[23]
Pirard, D., Vereecken, P., Melot, C. and Heenen, M. (2005) Three Percent Diclofenac in 2.5% Hyaluronan Gel in the Treatment of Actinic Keratosis: A Meta-Analysis of the Recent Studies. Archives of Dermatological Research, 297, 185-189. https://doi.org/10.1007/s00403-005-0601-9
[24]
Cham, B.E., Gilliver, M. and Wilson, L. (1987) Antitumour Effects of Glycoalkaloids Isolated from Solanum sodomaeum. Planta Medica, 53, 34-36. https://doi.org/10.1055/s-2006-962612
[25]
Cham, B.E., Daunter, B. and Evans, R. (1991) Topical Treatment of Malignant and Premalignant Skin Cancers by Very Low Concentrations of a Standard Mixture of Solasodine Glycosides. Cancer Letters, 59,183-192. https://doi.org/10.1016/0304-3835(91)90140-D
[26]
Daunter, B. and Cham, B.E. (1990) Solasodine Glycosides. In vitro Preferential Cytotoxicity for Human Cancer Cells. Cancer Letters, 55, 209-220. https://doi.org/10.1016/0304-3835(90)90121-D
[27]
Cham, B.E. (2013) Drug Therapy: Solamargine and Other Solasodine Rhamnosyl Glycosides as Anticancer Agents. Modern Chemotherapy, 2, 33-49. https://doi.org/10.4236/mc.2013.22005
[28]
Cham, B.E. (2008) Cancer Intralesion Chemotherapy with Solasodine Rhamnosyl Glycosides. Research Journal of Biological Sciences, 3, 1008-1017.
[29]
Millward, M., Powell, A., Tyson, S., Daly, P., Ferguson, R. and Carter, S. (2005) Phase 1 Trial of Coramsine (SBP002) in Patients with Advanced Solid Tumors. Journal of Clinical Oncology, 23, 3105. https://doi.org/10.1200/jco.2005.23.16_suppl.3105
[30]
Cham, B.E. and Daunter, B. (1990) Solasodine Glycosides. Selective Cytotoxicity for Cancer Cells and Inhibition of Cytotoxicity by Rhamnose in Mice with Sarcoma 180. Cancer Letters, 55, 221-225. https://doi.org/10.1016/0304-3835(90)90122-E
[31]
Punjabi, S., Cook, L.J., Kersey, P., Marks, R. and Cerio, R. (2008) Solasodine Glycoalkaloids: A Novel Topical Therapy for Basal Cell Carcinoma. A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicentre Study. International Journal of Dermatology, 47, 78-82. https://doi.org/10.1111/j.1365-4632.2007.03363.x
[32]
Cham, B.E. (2023) The Value of Excipients in Product Development, an Impactful Example of Curaderm, a Topical Skin Cancer Treatment.
[33]
Nistico, S., Del Duca, E., Torchia, V., Gliozzi, M., Bottoni, U. and Muscoli, C. (2018) Cost-Efficacy Analysis of 3% Diclofenac Sodium, Ingenol Mebutate, and 3.75% Imiquimod in the Treatment of Actinic Keratosis. International Journal of Immunopathology and Pharmacology, 31, 1-8. https://doi.org/10.1177/2058738418757925
[34]
Fleming, M. (2022) How Much Does It Cost to Treat Actinic Keratosis without Insurance in 2023? https://www.talktomira.com/post/how-much-does-it-cost-to-treat-actinic-keratosis-without-insurance-in-2022
