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Advances in Topical Treatments of Cutaneous Malignancies

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Abstract

Surgical excision has been the preferred treatment for cutaneous malignancies, but can be affected by various considerations. Noninvasive, self-administered topical treatments represent an alternative option. The aim of this review was to evaluate and summarize evidence-based recommendations for topical treatments of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), in situ melanoma (MIS), and extramammary Paget’s disease (EMPD). Studies were reviewed on PubMed. Included studies were summarized, assessed for biases, and assigned a level of evidence to develop treatment recommendations. For the treatment of superficial BCC, complete clearance rates ranged from 90 to 93% for 5% 5-fluorouracil (5-FU) and 71 to 76% for imiquimod (IMQ). For the treatment of nodular BCC, clearance rates for photodynamic therapy (PDT) were 91% at 3 months, with a sustained lesion clearance response rate of 76% after 5 years of follow-up. Clearance rates were 53 to 76% with IMQ. For squamous cell carcinoma in situ, clearance rates ranged from 52 to 98% for PDT, 67 to 92% for 5-FU, and 75 to 93% for IMQ. For MIS, clearance rates ranged from 53 to 92% for IMQ. For EMPD, 54% of 110 patients in cohort studies and case series had a clinical complete response with IMQ. While surgical intervention remains the standard of care for skin cancer, non-invasive, self-administered topical treatments are highly desirable alternative options. Ultimately, the patient and provider should find a treatment modality that aligns with the patient’s expectations and maintenance of quality of life.

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References

  1. Kim JYS, Kozlow JH, Mittal B, Moyer J, Olencki T, Rodgers P, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. 2018;78(3):540–59. https://doi.org/10.1016/j.jaad.2017.10.006.

    Article  Google Scholar 

  2. Kim JYS, Kozlow JH, Mittal B, Moyer J, Olenecki T, Rodgers P, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018;78(3):560–78. https://doi.org/10.1016/j.jaad.2017.10.007.

    Article  Google Scholar 

  3. Swetter SM, Tsao H, Bichakjian CK, Curiel-Lewandrowski C, Elder DE, Gershenwald JE, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80(1):208–50. https://doi.org/10.1016/j.jaad.2018.08.055.

    Article  Google Scholar 

  4. Thomas D, Zalcberg J. 5-fluorouracil: a pharmacological paradigm in the use of cytotoxics. Clin Exp Pharmacol Physiol. 1998;25(11):887–95. https://doi.org/10.1111/j.1440-1681.1998.tb02339.x.

    Article  CAS  Google Scholar 

  5. Gross K, Kircik L, Kricorian G. 5% 5-Fluorouracil cream for the treatment of small superficial Basal cell carcinoma: efficacy, tolerability, cosmetic outcome, and patient satisfaction. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2007;33(4):433–9. https://doi.org/10.1111/j.1524-4725.2007.33090.x (discussion 440).

    Article  CAS  Google Scholar 

  6. Efudex-40TM (fluorouracil topical cream) prescribing information. Costa Mesa (CA): Valeant Pharmaceuticals International; 2004.

  7. Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol. 2009;145(12):1431–8. https://doi.org/10.1001/archdermatol.2009.291.

    Article  CAS  Google Scholar 

  8. Pomerantz H, Hogan D, Eilers D, Swetter SM, Chen SC, Jacob SE, et al. Long-term efficacy of topical fluorouracil cream, 5%, for treating actinic keratosis: a randomized clinical trial. JAMA Dermatol. 2015;151(9):952. https://doi.org/10.1001/jamadermatol.2015.0502.

    Article  CAS  Google Scholar 

  9. Weinstock MA, Thwin SS, Siegel JA, Marcolivio K, Means AD, Leader NF, et al. Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: a randomized clinical trial. JAMA Dermatol. 2018;154(2):167. https://doi.org/10.1001/jamadermatol.2017.3631.

    Article  Google Scholar 

  10. Jansen MHE, Kessels JPHM, Nelemans PJ, Kouloubis N, Arits AHMM, van Pelt HPA, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380(10):935–46. https://doi.org/10.1056/NEJMoa1811850.

    Article  CAS  Google Scholar 

  11. Wu Y, Tang N, Cai L, Li Q. Relative efficacy of 5-fluorouracil compared with other treatments among patients with actinic keratosis: a network meta-analysis. Dermatol Ther. 2019. https://doi.org/10.1111/dth.12822.

    Article  Google Scholar 

  12. Gupta AK, Paquet M. Network meta-analysis of the outcome ‘participant complete clearance’ in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol. 2013;169(2):250–9. https://doi.org/10.1111/bjd.12343.

    Article  CAS  Google Scholar 

  13. Prince GT, Cameron MC, Fathi R, Alkousakis T. Topical 5-fluorouracil in dermatologic disease. Int J Dermatol. 2018;57(10):1259–64. https://doi.org/10.1111/ijd.14106.

    Article  CAS  Google Scholar 

  14. Gupta AK, Weiss JS, Jorizzo JL. 5-fluorouracil 0.5% cream for multiple actinic or solar keratoses of the face and anterior scalp. Skin Ther Lett. 2001;6(9):1–4.

    CAS  Google Scholar 

  15. Salim A, Leman JA, McColl JH, Chapman R, Morton CA. Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen’s disease. Br J Dermatol. 2003;148(3):539–43. https://doi.org/10.1046/j.1365-2133.2003.05033.x.

    Article  CAS  Google Scholar 

  16. Morton C, Horn M, Leman J, Tack B, Bedane C, Tjioe M, et al. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial. Arch Dermatol. 2006;142(6):729–35. https://doi.org/10.1001/archderm.142.6.729.

    Article  CAS  Google Scholar 

  17. Neale H, Michelon M, Jacob S, Pinkston M, Ukaegbu R, Zamor W, et al. Topical 5% 5-fluorouracil versus procedural modalities for squamous cell carcinoma in situ and superficial basal cell carcinoma: a retrospective cohort analysis. J Am Acad Dermatol. 2021. https://doi.org/10.1016/j.jaad.2021.08.045.

    Article  Google Scholar 

  18. Litwin MS, Ryan RF, Ichinose H, Reed RR, Kremetz ET. Proceedings: use of 5 fluorouracil in the topical therapy of skin cancer: a review of 157 patients. Proc Natl Cancer Conf. 1972;7:549–61.

    CAS  Google Scholar 

  19. Hamouda B, Jamila Z, Najet R, Slim T, Rafiaa N, Noureddine B, et al. Topical 5-fluorouracil to treat multiple or unresectable facial squamous cell carcinomas in xeroderma pigmentosum. J Am Acad Dermatol. 2001;44(6):1054. https://doi.org/10.1067/mjd.2001.113476.

    Article  CAS  Google Scholar 

  20. FDA Approves Calcipotriene for Plaque Psoriasis in Adolescents. Medscape. Accessed October 12, 2021. http://www.medscape.com/viewarticle/913407

  21. Rosenberg AR, Tabacchi M, Ngo KH, Wallendorf M, Rosman IS, Cornelius LA, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4(6): 125476. https://doi.org/10.1172/jci.insight.125476.

    Article  Google Scholar 

  22. Cunningham TJ, Tabacchi M, Eliane JP, Tuchayi SM, Manivasagam S, Mirzaalian H, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2016;127(1):106–16. https://doi.org/10.1172/JCI89820.

    Article  Google Scholar 

  23. Molina GE, Khalifian S, Mull JL, Chen L, Rosman IS, Faulkner-Jones BE, et al. Topical combination of fluorouracil and calcipotriene as a palliative therapy for refractory extramammary paget disease. JAMA Dermatol. 2019;155(5):599–603. https://doi.org/10.1001/jamadermatol.2018.4793.

    Article  Google Scholar 

  24. Sauder DN. Immunomodulatory and pharmacologic properties of imiquimod. J Am Acad Dermatol. 2000;43(1 Pt 2):S6-11. https://doi.org/10.1067/mjd.2000.107808.

    Article  CAS  Google Scholar 

  25. Vun Y, Siller G. Use of 5% imiquimod cream in the treatment of facial basal cell carcinoma: a 3-year retrospective follow-up study. Australas J Dermatol. 2006;47(3):169–71. https://doi.org/10.1111/j.1440-0960.2006.00265.x.

    Article  Google Scholar 

  26. Korman N, Moy R, Ling M, Matheson R, Smith S, McKane S, et al. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol. 2005;141(4):467–73. https://doi.org/10.1001/archderm.141.4.467.

    Article  CAS  Google Scholar 

  27. 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(9):1165–71. https://doi.org/10.1001/archderm.138.9.1165.

    Article  CAS  Google Scholar 

  28. Schulze HJ, Cribier B, Requena L, Reifenberger J, Ferrándiz C, Garcia Diez A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol. 2005;152(5):939–47. https://doi.org/10.1111/j.1365-2133.2005.06486.x.

    Article  CAS  Google Scholar 

  29. Beutner KR, Geisse JK, Helman D, Fox TL, Ginkel A, Owens ML. Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol. 1999;41(6):1002–7. https://doi.org/10.1016/s0190-9622(99)70261-6.

    Article  CAS  Google Scholar 

  30. Garcia-Martin E, Gil-Arribas LM, Idoipe M, Alfaro J, Pueyo V, Pablo LE, et al. Comparison of imiquimod 5% cream versus radiotherapy as treatment for eyelid basal cell carcinoma. Br J Ophthalmol. 2011;95(10):1393–6. https://doi.org/10.1136/bjo.2010.193078.

    Article  CAS  Google Scholar 

  31. Geisse J, Caro I, Lindholm J, Golitz L, Stampone P, Owens M. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol. 2004;50(5):722–33. https://doi.org/10.1016/j.jaad.2003.11.066.

    Article  Google Scholar 

  32. Jia HX, He YL. Efficacy and safety of imiquimod 5% cream for basal cell carcinoma: a meta-analysis of randomized controlled trial. J Dermatol Treat. 2020;31(8):831–8. https://doi.org/10.1080/09546634.2019.1638883.

    Article  Google Scholar 

  33. 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(3):390–8. https://doi.org/10.1067/mjd.2002.126215.

    Article  Google Scholar 

  34. Butler DF, Parekh PK, Lenis A. Imiquimod 5% cream as adjunctive therapy for primary, solitary, nodular nasal basal cell carcinomas before Mohs micrographic surgery: a randomized, double blind, vehicle-controlled study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2009;35(1):24–9. https://doi.org/10.1111/j.1524-4725.2008.34378.x.

    Article  CAS  Google Scholar 

  35. Sterry W, Ruzicka T, Herrera E, Takwale A, Bichel J, Andres K, et al. Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion. Br J Dermatol. 2002;147(6):1227–36. https://doi.org/10.1046/j.1365-2133.2002.05069.x.

    Article  CAS  Google Scholar 

  36. Eigentler TK, Kamin A, Weide BM, Breuninger H, Caroli UM, Möhrle M, et al. A phase III, randomized, open label study to evaluate the safety and efficacy of imiquimod 5% cream applied thrice weekly for 8 and 12 weeks in the treatment of low-risk nodular basal cell carcinoma. J Am Acad Dermatol. 2007;57(4):616–21. https://doi.org/10.1016/j.jaad.2007.05.022.

    Article  Google Scholar 

  37. Peris K, Campione E, Micantonio T, Marulli GC, Fargnoli MC, Chimenti S. Imiquimod treatment of superficial and nodular basal cell carcinoma: 12-week open-label trial. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2005;31(3):318–23. https://doi.org/10.1111/j.1524-4725.2005.31081.

    Article  CAS  Google Scholar 

  38. Bath-Hextall F, Ozolins M, Armstrong SJ, Colver GB, Perkins W, Miller PSJ, et al. Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial. Lancet Oncol. 2014;15(1):96–105. https://doi.org/10.1016/S1470-2045(13)70530-8.

    Article  CAS  Google Scholar 

  39. Sinx KAE, Nelemans PJ, Kelleners-Smeets NWJ, Winnepenninckx VJL, Arits AHMM, Mosterd K. Surgery versus combined treatment with curettage and imiquimod for nodular basal cell carcinoma: One-year results of a noninferiority, randomized, controlled trial. J Am Acad Dermatol. 2020;83(2):469–76. https://doi.org/10.1016/j.jaad.2020.04.053.

    Article  CAS  Google Scholar 

  40. Tiodorovic-Zivkovic D, Zalaudek I, Longo C, De Pace B, Albertini G, Argenziano G. Successful treatment of two invasive squamous cell carcinomas with topical 5% imiquimod cream in elderly patients. Eur J Dermatol EJD. 2012;22(4):579–80. https://doi.org/10.1684/ejd.2012.1771.

    Article  Google Scholar 

  41. Dirschka T, Schmitz L, Bartha Á. Clinical and histological resolution of invasive squamous cell carcinoma by topical imiquimod 3.75%: a case report. Eur J Dermatol EJD. 2016;26(4):408–9. https://doi.org/10.1684/ejd.2016.2788.

    Article  Google Scholar 

  42. Patel GK, Goodwin R, Chawla M, Laidler P, Price PE, Finlay AY, et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2006;54(6):1025–32. https://doi.org/10.1016/j.jaad.2006.01.055.

    Article  Google Scholar 

  43. Baiocchi G, Begnami MDFS, Fukazawa EM, Surima WS, Badiglian-Filho L, Costa FD, et al. Conservative management of extramammary paget disease with imiquimod. J Low Genit Tract Dis. 2012;16(1):59–63. https://doi.org/10.1097/LGT.0b013e31822d2484.

    Article  Google Scholar 

  44. Wilmer EN, Gustafson CJ, Ahn CS, Davis SA, Feldman SR, Huang WW. Most common dermatologic conditions encountered by dermatologists and nondermatologists. Cutis. 2014;94(6):285–92.

    Google Scholar 

  45. Blauvelt A, Kempers S, Lain E, Schlesinger T, Tyring S, Forman S, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384(6):512–20. https://doi.org/10.1056/NEJMoa2024040.

    Article  CAS  Google Scholar 

  46. Wolf JE, Taylor JR, Tschen E, Kang S. Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol. 2001;40(11):709–13. https://doi.org/10.1046/j.1365-4362.2001.01324.x.

    Article  CAS  Google Scholar 

  47. Rivers JK, Arlette J, Shear N, Guenther L, Carey W, Poulin Y. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol. 2002;146(1):94–100. https://doi.org/10.1046/j.1365-2133.2002.04561.x.

    Article  CAS  Google Scholar 

  48. Fecker LF, Stockfleth E, Nindl I, Ulrich C, Forschner T, Eberle J. The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti-inflammatory drugs (NSAIDs). Br J Dermatol. 2007;156(Suppl 3):25–33. https://doi.org/10.1111/j.1365-2133.2007.07856.x.

    Article  CAS  Google Scholar 

  49. Barker N, Clevers H. Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov. 2006;5(12):997–1014. https://doi.org/10.1038/nrd2154.

    Article  CAS  Google Scholar 

  50. Tjiu JW, Liao YH, Lin SJ, Huang YL, Tsai WL, Chu CY, et al. Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis. J Invest Dermatol. 2006;126(5):1143–51. https://doi.org/10.1038/sj.jid.5700191.

    Article  CAS  Google Scholar 

  51. Brinkhuizen T, Frencken KJA, Nelemans PJ, Hoff MLS, Kelleners-Smeets NWJ, Zur Hausen A, et al. The effect of topical diclofenac 3% and calcitriol 3 μg/g on superficial basal cell carcinoma (sBCC) and nodular basal cell carcinoma (nBCC): a phase II, randomized controlled trial. J Am Acad Dermatol. 2016;75(1):126–34. https://doi.org/10.1016/j.jaad.2016.01.050.

    Article  CAS  Google Scholar 

  52. Heppt MV, Leiter U, Steeb T, Amaral T, Bauer A, Becker JC, et al. S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma—short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators. J Dtsch Dermatol Ges J Ger Soc Dermatol JDDG. 2020;18(3):275–94. https://doi.org/10.1111/ddg.14048.

    Article  Google Scholar 

  53. Pflugfelder A, Welter AK, Leiter U, Weide B, Held L, Eigentler TK, et al. Open label randomized study comparing 3 months vs. 6 months treatment of actinic keratoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of the German Dermatologic Cooperative Oncology Group. J Eur Acad Dermatol Venereol JEADV. 2012;26(1):48–53. https://doi.org/10.1111/j.1468-3083.2011.04005.x.

    Article  CAS  Google Scholar 

  54. Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol. 1992;55(1):145–57. https://doi.org/10.1111/j.1751-1097.1992.tb04222.x.

    Article  CAS  Google Scholar 

  55. Gold MH. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part five of a five-part series: ALA-PDT and MAL-PDT What Makes Them Different. J Clin Aesthetic Dermatol. 2009;2(2):44–7.

    Google Scholar 

  56. Braathen LR, Szeimies RM, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, et al. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. 2007;56(1):125–43. https://doi.org/10.1016/j.jaad.2006.06.006.

    Article  Google Scholar 

  57. Zane C, Capezzera R, Sala R, Venturini M, Calzavara-Pinton P. Clinical and echographic analysis of photodynamic therapy using methylaminolevulinate as sensitizer in the treatment of photodamaged facial skin. Lasers Surg Med. 2007;39(3):203–9. https://doi.org/10.1002/lsm.20470.

    Article  Google Scholar 

  58. Wiegell SR, Wulf HC. Photodynamic therapy of acne vulgaris using methyl aminolaevulinate: a blinded, randomized, controlled trial. Br J Dermatol. 2006;154(5):969–76. https://doi.org/10.1111/j.1365-2133.2005.07107.x.

    Article  CAS  Google Scholar 

  59. Wan MT, Lin JY. Current evidence and applications of photodynamic therapy in dermatology. Clin Cosmet Investig Dermatol. 2014;7:145–63. https://doi.org/10.2147/CCID.S35334.

    Article  Google Scholar 

  60. Thomson J, Hogan S, Leonardi-Bee J, Williams HC, Bath-Hextall FJ. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2020;11: CD003412. https://doi.org/10.1002/14651858.CD003412.pub3.

    Article  Google Scholar 

  61. Matei C, Tampa M, Poteca T, Panea-Paunica G, Georgescu SR, Ion RM, et al. Photodynamic therapy in the treatment of basal cell carcinoma. J Med Life. 2013;6(1):50–4.

    CAS  Google Scholar 

  62. Fink-Puches R, Soyer HP, Hofer A, Kerl H, Wolf P. Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy. Arch Dermatol. 1998;134(7):821–6. https://doi.org/10.1001/archderm.134.7.821.

    Article  CAS  Google Scholar 

  63. Cohen D, Lee P. Photodynamic therapy for non-melanoma skin cancers. Cancers. 2016;8(10):90. https://doi.org/10.3390/cancers8100090.

    Article  CAS  Google Scholar 

  64. Savoia P, Deboli T, Previgliano A, Broganelli P. Usefulness of photodynamic therapy as a possible therapeutic alternative in the treatment of basal cell carcinoma. Int J Mol Sci. 2015;16(10):23300–17. https://doi.org/10.3390/ijms161023300.

    Article  CAS  Google Scholar 

  65. Rhodes LE, de Rie MA, Leifsdottir R, Yu RC, Bachmann I, Goulden V, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol. 2007. https://doi.org/10.1001/archderm.143.9.1131.

    Article  Google Scholar 

  66. 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(3):605–8. https://doi.org/10.1038/bjc.1994.112.

    Article  CAS  Google Scholar 

  67. Zaar O, Fougelberg J, Hermansson A, Gillstedt M, Wennberg-Larkö AM, Paoli J. Effectiveness of photodynamic therapy in Bowen’s disease: a retrospective observational study in 423 lesions. J Eur Acad Dermatol Venereol. 2017;31(8):1289–94. https://doi.org/10.1111/jdv.14164.

    Article  CAS  Google Scholar 

  68. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma—PubMed. https://pubmed-ncbi-nlm-nih-gov.evms.idm.oclc.org/17875873/. Accessed 9 Aug 2021.

  69. Wulf HC. Photodynamic therapy in daylight for actinic keratoses. JAMA Dermatol. 2016;152(6):631–2. https://doi.org/10.1001/jamadermatol.2015.5979.

    Article  Google Scholar 

  70. Rubel DM, Spelman L, Murrell DF, See JA, Hewitt D, Foley P, et al. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol. 2014;171(5):1164–71. https://doi.org/10.1111/bjd.13138.

    Article  CAS  Google Scholar 

  71. Sotiriou E, Evangelou G, Papadavid E, Apalla Z, Vrani F, Vakirlis E, et al. Conventional vs daylight photodynamic therapy for patients with actinic keratosis on face and scalp: 12-month follow-up results of a randomized, intra-individual comparative analysis. J Eur Acad Dermatol Venereol JEADV. 2018;32(4):595–600. https://doi.org/10.1111/jdv.14613.

    Article  CAS  Google Scholar 

  72. Wiegell SR, Skødt V, Wulf HC. Daylight-mediated photodynamic therapy of basal cell carcinomas—an explorative study. J Eur Acad Dermatol Venereol JEADV. 2014;28(2):169–75. https://doi.org/10.1111/jdv.12076.

    Article  CAS  Google Scholar 

  73. Gilbert SM, Gidley Baird A, Glazer S, Barden JA, Glazer A, Teh LC, et al. A phase I clinical trial demonstrates that nfP2X 7-targeted antibodies provide a novel, safe and tolerable topical therapy for basal cell carcinoma. Br J Dermatol. 2017;177(1):117–24. https://doi.org/10.1111/bjd.15364.

    Article  CAS  Google Scholar 

  74. Kim J, Tang JY, Gong R, Kim J, Lee JJ, Clemons KV, et al. Itraconazole, a commonly used antifungal that inhibits hedgehog pathway activity and cancer growth. Cancer Cell. 2010;17(4):388–99. https://doi.org/10.1016/j.ccr.2010.02.027.

    Article  CAS  Google Scholar 

  75. Kim DJ, Kim J, Spaunhurst K, Montoya J, Khodosh R, Chandra K, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(8):745–51. https://doi.org/10.1200/JCO.2013.49.9525.

    Article  CAS  Google Scholar 

  76. Ally MS, Ransohoff K, Sarin K, Atwood SX, Rezaee M, Bailey-Healy I, et al. Effects of combined treatment with arsenic trioxide and itraconazole in patients with refractory metastatic basal cell carcinoma. JAMA Dermatol. 2016;152(4):452–6. https://doi.org/10.1001/jamadermatol.2015.5473.

    Article  Google Scholar 

  77. Girardi D, Barrichello A, Fernandes G, Pereira A. Targeting the hedgehog pathway in cancer: current evidence and future perspectives. Cells. 2019;8(2):E153. https://doi.org/10.3390/cells8020153.

    Article  CAS  Google Scholar 

  78. PellePharm, Inc. Double-Blind, Randomized, Vehicle-Controlled Proof of Concept Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients. clinicaltrials.gov; 2020. https://clinicaltrials.gov/ct2/show/NCT02762084. Accessed 15 Jun 2022.

  79. PellePharm, Inc. A Phase 3, Multicenter, Open-Label Extension Study of Patidegib Topical Gel, 2% in Subjects With Gorlin Syndrome (Basal Cell Nevus Syndrome). clinicaltrials.gov; 2021. https://clinicaltrials.gov/ct2/show/NCT04308395. Accessed 15 Nov 2021.

  80. Dantal J, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, et al. Sirolimus for secondary prevention of skin cancer in kidney transplant recipients: 5-year results. J Clin Oncol. 2018;36(25):2612–20. https://doi.org/10.1200/JCO.2017.76.6691.

    Article  CAS  Google Scholar 

  81. Euvrard S, Ulrich C, Lefrancois N. Immunosuppressants and skin cancer in transplant patients: focus on rapamycin. Dermatol Surg. 2004;30(4p2):628–33. https://doi.org/10.1111/j.1524-4725.2004.30148.x.

    Article  Google Scholar 

  82. Palvella Therapeutics, Inc. A Multicenter, Phase 2B, Randomized, Double-Blind, Stratified, Vehicle-Controlled Study Evaluating The Safety And Efficacy Of QTORIN 3.9% Sirolimus Topical Gel In Prevention Of BCCs In Patients With Gorlin Syndrome. clinicaltrials.gov; 2021. https://clinicaltrials.gov/ct2/show/NCT04893486. Accessed 24 Feb 2022

  83. Berg, LLC. Dose-Ranging Clinical Trial of Topical Creams Containing API 31510 for the Treatment of Superficial Basal Cell Carcinoma. clinicaltrials.gov; 2019. https://clinicaltrials.gov/ct2/show/results/NCT00604890. Accessed 14 Oct 2021.

  84. Arits AHMM, Mosterd K, Essers BA, Spoorenberg E, Sommer A, De Rooij MJM, et al. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial. Lancet Oncol. 2013;14(7):647–54. https://doi.org/10.1016/S1470-2045(13)70143-8.

    Article  CAS  Google Scholar 

  85. Roozeboom MH, Arits AHMM, Mosterd K, Sommer A, Essers BAB, de Rooij MJM, et al. Three-year follow-up results of photodynamic therapy vs. imiquimod vs. fluorouracil for treatment of superficial basal cell carcinoma: a single-blind, noninferiority, randomized controlled trial. J Invest Dermatol. 2016;136(8):1568–74. https://doi.org/10.1016/j.jid.2016.03.043.

    Article  CAS  Google Scholar 

  86. Jansen MHE, Mosterd K, Arits AHMM, Roozeboom MH, Sommer A, Essers BAB, et al. Five-year results of a randomized controlled trial comparing effectiveness of photodynamic therapy, topical imiquimod, and topical 5-fluorouracil in patients with superficial basal cell carcinoma. J Invest Dermatol. 2018;138(3):527–33. https://doi.org/10.1016/j.jid.2017.09.033.

    Article  CAS  Google Scholar 

  87. Rhodes LE, de Rie MA, Leifsdottir R, Yu RC, Bachmann I, Goulden V, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol. 2007;143(9):1131–6. https://doi.org/10.1001/archderm.143.9.1131.

    Article  CAS  Google Scholar 

  88. Morton C, Szeimies RM, Sidoroff A, Wennberg AM, Basset-Seguin N, Calzavara-Pinton P, et al. European Dermatology Forum Guidelines on topical photodynamic therapy. Eur J Dermatol EJD. 2015;25(4):296–311. https://doi.org/10.1684/ejd.2015.2570.

    Article  Google Scholar 

  89. Lansbury L, Bath-Hextall F, Perkins W, Stanton W, Leonardi-Bee J. Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies. BMJ. 2013;347: f6153. https://doi.org/10.1136/bmj.f6153.

    Article  Google Scholar 

  90. Rosen T, Harting M, Gibson M. Treatment of Bowen’s disease with topical 5% imiquimod cream: retrospective study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2007;33(4):427–31. https://doi.org/10.1111/j.1524-4725.2007.33089.x (discussion 431–432).

    Article  CAS  Google Scholar 

  91. Mackenzie-Wood A, Kossard S, de Launey J, Wilkinson B, Owens ML. Imiquimod 5% cream in the treatment of Bowen’s disease. J Am Acad Dermatol. 2001;44(3):462–70. https://doi.org/10.1067/mjd.2001.111335.

    Article  CAS  Google Scholar 

  92. Bargman H, Hochman J. Topical treatment of Bowen’s disease with 5-Fluorouracil. J Cutan Med Surg. 2003;7(2):101–5. https://doi.org/10.1007/s10227-002-0158-6.

    Article  Google Scholar 

  93. Morton C, Horn M, Leman J, Tack B, Bédane C, Tjioe M, et al. A placebo controlled European study comparing MAL-PDT with cryotherapy and 5-fluoracil in patients with Bowen’s disease: P09. 89. J Eur Acad Dermatol Venereol. 2004;18.

  94. Treatment and prognosis of low-risk cutaneous squamous cell carcinoma (cSCC)—UpToDate. https://www-uptodate-com.evms.idm.oclc.org/contents/treatment-and-prognosis-of-low-risk-cutaneous-squamous-cell-carcinoma-cscc?search=Treatment%20and%20prognosis%20of%20low-risk%20cutaneous%20squamous%20cell%20carcinoma%20(cSCC)&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed 26 Dec 2021.

  95. Ly L, Kelly JW, O’Keefe R, Sutton T, Dowling JP, Swain S, et al. Efficacy of imiquimod cream, 5%, for lentigo maligna after complete excision: a study of 43 patients. Arch Dermatol. 2011;147(10):1191–5. https://doi.org/10.1001/archdermatol.2011.260.

    Article  CAS  Google Scholar 

  96. Kirtschig G, van Meurs T, van Doorn R. Twelve-week treatment of lentigo maligna with imiquimod results in a high and sustained clearance rate. Acta Derm Venereol. 2015;95(1):83–5. https://doi.org/10.2340/00015555-1861.

    Article  CAS  Google Scholar 

  97. Wong JG, Toole JWP, Demers AA, Musto G, Wiseman MC. Topical 5% imiquimod in the treatment of lentigo maligna. J Cutan Med Surg. 2012;16(4):245–9. https://doi.org/10.1177/120347541201600405.

    Article  CAS  Google Scholar 

  98. Read T, Noonan C, David M, Wagels M, Foote M, Schaider H, et al. A systematic review of non-surgical treatments for lentigo maligna. J Eur Acad Dermatol Venereol JEADV. 2016;30(5):748–53. https://doi.org/10.1111/jdv.13252.

    Article  CAS  Google Scholar 

  99. Swetter SM, Chen FW, Kim DD, Egbert BM. Imiquimod 5% cream as primary or adjuvant therapy for melanoma in situ, lentigo maligna type. J Am Acad Dermatol. 2015;72(6):1047–53. https://doi.org/10.1016/j.jaad.2015.02.008.

    Article  CAS  Google Scholar 

  100. Mora AN, Karia PS, Nguyen BM. A quantitative systematic review of the efficacy of imiquimod monotherapy for lentigo maligna and an analysis of factors that affect tumor clearance. J Am Acad Dermatol. 2015;73(2):205–12. https://doi.org/10.1016/j.jaad.2015.05.022.

    Article  CAS  Google Scholar 

  101. Tio D, van der Woude J, Prinsen CAC, Jansma EP, Hoekzema R, van Montfrans C. A systematic review on the role of imiquimod in lentigo maligna and lentigo maligna melanoma: need for standardization of treatment schedule and outcome measures. J Eur Acad Dermatol Venereol JEADV. 2017;31(4):616–24. https://doi.org/10.1111/jdv.14085.

    Article  CAS  Google Scholar 

  102. Powell AM, Robson AM, Russell-Jones R, Barlow RJ. Imiquimod and lentigo maligna: a search for prognostic features in a clinicopathological study with long-term follow-up. Br J Dermatol. 2009;160(5):994–8. https://doi.org/10.1111/j.1365-2133.2009.09032.x.

    Article  CAS  Google Scholar 

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Algarin, Y.A., Jambusaria-Pahlajani, A., Ruiz, E. et al. Advances in Topical Treatments of Cutaneous Malignancies. Am J Clin Dermatol 24, 69–80 (2023). https://doi.org/10.1007/s40257-022-00731-x

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