Combination Topical Chemotherapy for the Treatment of an Invasive Cutaneous Squamous Cell Carcinoma

February 2020 | Volume 19 | Issue 2 | Case Reports | 202 | Copyright © February 2020


Published online January 17, 2020

Rachel Fayne , Sonali Nanda , Anna Nichols , John Shen

aDepartment of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL bShen Dermatology, Temecula, CA *These two authors contributed equally.

are still less effective than surgery when used as monotherapy. 4,5 Because these two drugs act through distinct mechanisms of action, combination therapy is a reasonable means to optimize outcomes for patients who wish to avoid surgery.21

The third topical agent used, tretinoin, is known to interfere with carcinogenesis and apoptosis. It is a retinoid, or a vitamin-A derivative, that acts on nuclear retinoic acid receptors in order to control cellular proliferation and differentiation.15 Topical tretinoin has been studied for its potential role as a chemopreventive agent for BCC and SCC, but thus far has been proven ineffective [24]. One study in renal transplant patients, with increased risk for SCC, showed that a combination of topical tretinoin and low dose systemic retinoids, in an attempt to lessen toxicity associated with high dose systemic retinoids, reduced the number of existing SCCs and reduced risk of new SCCs.25 While efficacy of topical tretinoin as monotherapy for SCC has not been studied, a combination of topical tretinoin, imiquimod and 5-FU, each with their distinct mechanisms of action, may provide improved long-term tumor free survival compared to single-drug regimens for patients with invasive SCC.

We present a patient with invasive SCC successfully treated with combination topical therapy consisting of 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream. Previous reports of the use of single-drug topical therapy with imiquimod or 5-FU in the treatment of SCC in situ shown promising results, however the success rates were still lower than surgical management. We demonstrate that the combination of these three medications provided an excellent outcome in our case, although the follow-up was only 25 months. Prospective randomized clinical trials are needed to support these findings, which may offer patients a non-surgical alternative to the current standard of care.

DISCLOSURES

The authors have no potential conflicts of interest, financial interests, relationships or affiliations relevant to the subject of this submission.

REFERENCES

1. Nehal KS, Bichakjian CK. Update on keratinocyte carcinomas. N Engl J Med. 2018;379(4):363-374.

2. Chitwood K, J. Etzkorn, and G. Cohen, Topical and intralesional treatment of nonmelanoma skin cancer: efficacy and cost comparisons. Dermatol Surg. 2013;39(9):1306-16.

3. Collins, A., J. Savas, and L. Doerfler. Nonsurgical treatments for nonmelanoma skin cancer. Dermatol Clin. 2019. 37(4):435-441.

4. Williams, H.C., et al., Surgery versus 5% imiquimod for nodular and superficial basal cell carcinoma: 5-year results of the SINS randomized controlled trial. J Invest Dermatol. 2017. 137(3):614-619.

5. Jansen, M.H.E., 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): p. 527-533.

6. Quirk, C., et al., Sustained clearance of superficial basal cell carcinomas treated with imiquimod cream 5%: results of a prospective 5-year study. Cutis. 2010. 85(6): p. 318-24.

7. Bath-Hextall, F., 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.

8. Guy, G.P., Jr., et al., Vital signs: melanoma incidence and mortality trends and projections - United States, 1982-2030. MMWR Morb Mortal Wkly Rep, 2015. 64(21): p. 591-6.

9. Rogers, H.W., et al., Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA Dermatol. 2015. 151(10):1081-6.

10. Muzic, J.G., et al., Incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: a population-based study in olmsted county, Minnesota, 2000 to 2010. Mayo Clin Proc. 2017. 92(6):890-898.

11. Regula, C.G., et al., Functionality of patients 75 years and older undergoing mohs micrographic surgery: a multicenter study. Dermatol Surg. 2017. 43(7):904-910.

12. Rogers EM, et al. Comorbidity scores associated with limited life expectancy in the very elderly with nonmelanoma skin cancer. J Am Acad Dermatol. 2018. 78(6):1119-1124.

13. Chauhan R, et al. Age at Diagnosis as a relative contraindication for intervention in facial nonmelanoma skin cancer. JAMA Surg. 2018. 153(4):390-392.

14. Sobanko, JF, et al. Importance of physical appearance in patients with skin cancer. Dermatol Surg. 2015. 41(2):183-8.

15. Micali G, et al. Topical pharmacotherapy for skin cancer: part I. Pharmacology. J Am Acad Dermatol. 2014. 70(6):965 e1-12; quiz 977-8.

16. Peris K, et al., Imiquimod treatment of superficial and nodular basal cell carcinoma: 12-week open-label trial. Dermatol Surg. 2005. 31(3):318-23.

17. Nouri K, C. O'Connell, and M.P. Rivas, Imiquimod for the treatment of Bowen's disease and invasive squamous cell carcinoma. J Drugs Dermatol. 2003. 2(6): p. 669-73.

18. Goette DK. Treatment of keratoacanthoma with topical fluorouracil. Arch Dermatol. 1983. 119(11):951-3.

19. Kiss N, et al. Intralesional therapy for the treatment of keratoacanthoma. Dermatol Ther. 2019. 32(3):e12872.

20. Arits AH, 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.

21. Shaw FM and M.A. Weinstock, Comparing topical treatments for basal cell carcinoma. J Invest Dermatol. 2018. 138(3):484-486.

22. Tinelli M, et al. What determines patient preferences for treating low risk basal cell carcinoma when comparing surgery vs imiquimod? A discrete choice experiment survey from the SINS trial. BMC Dermatol. 2012. 12:19.

23. Yoon J, et al. Impact of topical fluorouracil cream on costs of treating keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis. J Am Acad Dermatol. 2018. 79(3): p. 501-507 e2.

24. Weinstock MA, et al. Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial. J Invest Dermatol. 2012. 132(6):1583-90.

25. Rook AH, et al., Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients. Transplantation. 1995. 59(5):714-9.

AUTHOR CORRESPONDENCE