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 BA,*a Sonali Nanda MS,*a Anna Nichols MD PhD,a John Shen MDb

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

INTRODUCTION: Standard of care for squamous cell carcinoma (SCC) is usually surgical, with either excision or Mohs micrographic surgery. However, surgery may not be ideal for elderly patients with numerous lesions, who are poor surgical candidates or who refuse surgery. Topical 5-fluorouracil (5-FU) and imiquimod have been studied off-label as monotherapies in the treatment of SCC in situ with promising results. However, long-term tumor-free survival rates are still less than with surgical management.

METHODS: We report a case of biopsy-proven invasive SCC in an 86-year-old Caucasian male with history of multiple actinic keratoses and no previous skin cancers. The patient declined surgical treatment due to concerns about cosmetic outcomes. A combination of topical 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream was used five nights per week under occlusion for a treatment goal of 30 total applications. The patient was evaluated in clinic every 2 weeks during which the site was treated with cryotherapy. The patient reported burning pain associated with treatment and only completed 24 of the 30 applications.

RESULTS: Follow-up biopsy 15 months after completing topical treatment revealed dermal scar with no evidence of residual carcinoma.

CONCLUSION: Topical combination therapy with imiquimod, 5-FU, and tretinoin with intermittent, brief cryotherapy effectively treated a small, invasive SCC in this select patient who deferred surgery. Prospective randomized-controlled clinical trials to assess the role of combination topical treatment for invasive SCCs are warranted.

J Drugs Dermatol. 2020;19(2)202-204 doi:10.36849/JDD.2020.2228


Standard of care for the treatment of SCC is either surgical excision, Mohs micrographic surgery or radiation therapy (RT) in cases where surgery is not ideal.1 Outcomes for patients with SCC are excellent in terms of survival.1 However, surgery may not be the best option for patients with numerous or extensive lesions, elderly patients, or patients who are concerned about their cosmetic outcome. Less invasive treatment options include injectable medications such as 5-FU, methotrexate, bleomycin and interferon, photodynamic therapy (PDT), cryotherapy or RT.2,3 Several topical medications have been used off-label to treat SCC in situ, including the topical chemotherapeutic agent 5-FU, which interferes with DNA synthesis, and the topical immunomodulator imiquimod, which regulates the immune response.4-7 However, long-term tumor-free survival rates are lower than with surgery.7 Here, we present a case of biopsy-proven SCC treated with a combination topical regimen that resulted in clinical resolution of the lesion during the 25-month follow-up period.


An 86-year-old Caucasian male with a previous history of actinic keratoses on the scalp, and no prior history of skin cancer, presented with a tender, crusted pink papule, approximately 3 mm in diameter, on his right posterior ear (Figure 1A). Pathology confirmed invasive SCC described as atypical squamous cells with scattered mitotic figures extending in strands within the dermis. The epidermis demonstrated papillomatosis with pseudo-horn cyst formation (Figure 2A-B). The patient was extremely concerned with the cosmetic outcome of surgical treatment and sought alternative options, thus a non-surgical treatment plan was employed using a combination of off-label topical treatments used frequently as monotherapy for superficial BCC or SCC in situ in patients who defer surgery. The treatment goal