Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Nonmelanoma Skin Cancers

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• In this retrospective analysis aimed at evaluating the efficacy of combining topical antitumor medications, 133 patients with 186 skin cancers (97 basal cell carcinomas [BCCs] and 89 squamous cell carcinomas [SCCs]) were treated with either imiquimod/tretinoin (IMI/TRET), 5-fluorouracil/tretinoin (5-FU/TRET), or imiquimod/5-fluorouracil/tretinoin (IMI/5-FU/TRET) plus cryotherapy every 2 weeks. For BCC, rates of clearance were 94%, 85%, and 97% for IMI/TRET, 5-FU/TRET, and IMI/5-FU/TRET, respectively. There were 6 recurrences of BCC, 5 of which occurred on the head and neck region. Clearance rates for SCC were 95%, 73%, and 100% for IMI/TRET, 5-FU/TRET, and IMI/5-FU/TRET, respectively, and 6 recurrences of SCC occurred during the follow-up period.

• Treatment with IMI/5-FU/TRET was the most effective topical combination therapy for nonmelanoma skin cancers. This could be a treatment option for patients who are unwilling to undergo surgery or who cannot afford expensive surgical procedures.

– Caroline K. Crabtree, MD

Written by

 

 

Roger I. Ceilley MD

There is an increasing need for effective nonsurgical treatments for nonmelanoma skin cancers. We are seeing more patients with "surgical fatigue" requesting other approaches. Our clinic utilizes a number of approaches, including curettage and imiquimod; cryosurgery (alone or with intralesional 5-FU or methotrexate); PDT with 5-FU; as well as 5-FU and imiquimod in combination. We find these most useful with superficial and lower-extremity lesions.

Without knowing the biopsy margin status, it is difficult to tell how well the various treatments work. Treatment with electrodessication and curettage or cryo-destruction alone would likely give similar results and be less traumatic and less expensive than cryosurgery every 2 weeks plus medicine costs. The cost of time and travel for the treatments may be quite significant as well.

To adequately understand the benefit of the combination therapies over individual therapies, controlled studies are needed. Using treatment arms with each of these combination therapies would be most useful. Follow-up should be a minimum of 5 years for solid conclusions, especially for invasive tumors.

Abstract

BACKGROUND

Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. 

OBJECTIVE

We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. 

METHODS

This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. 

RESULTS

A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). 

CONCLUSIONS

The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. 

Journal of Drugs in Dermatology

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers

J Drugs Dermatol 2021 Jan 28;20(3)5427-33, WJ Nahm, J Shen, PM Zito, AM Gonzalez, N Nagrani, K Moore, EV Badiavas, RS Kirsner, AJ Nichols 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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