Topical sirolimus may benefit solid-organ transplant recipients as a chemopreventive agent

Chong S, Wong HY, Althabteh A, Cox C, Stevenson P, Brown S, Griffin A, Isbel N, Siller G, Soyer HP, Schaider H, Roy E, Campbell S, Green AC, Khosrotehrani K, Chemoprevention of cutaneous squamous cell carcinoma and its precursors in solid organ transplant recipients using topical sirolimus: a randomized, double-blind, placebo-controlled pilot trial, Journal of the American Academy of Dermatology (2022), doi: https://doi.org/10.1016/j.jaad.2022.02.039.

Among 29 patients (mean age of 61.8 years) that were enrolled, the number of keratotic lesions was reduced by ~31% (p=.0001) on the treated side but increased on the contralateral hand/forearm that received a vehicle gel.

Clinical Pearls

• The was a 12-week randomized, double-blind, vehicle-controlled pilot study to determine if once-daily sirolimus topically-applied to dorsal hand and forearm could decrease the incidence of cutaneous squamous cell carcinoma (cSCC) in patients with a history of non-melanoma skin cancers (NMSCs).

• The authors found that among 29 patients mean age of 61.8 years that were enrolled the number of keratotic lesions was reduced by ~31% (p=.0001) on the treated side but increased on the contralateral hand/forearm that received a vehicle gel.

• Over 25.5 month follow up, there was an 81% decrease in intraepithelial carcinomas on the treated side vs. non-treated side.

• 38% discontinued the study early due to: convenience (n=5), unrelated adverse events (n=5), contact dermatitis (n=1) after ~5 weeks of topical sirolimus use.

Discussion:

Nonmelanoma skin cancers (NMSCs) such as cutaneous squamous cell carcinoma (cSCC) affect over 3 million patients annually. If caught early, NMSCs are usually curable with surgical resection and close follow-up. Individuals who are solid-organ transplant recipients (SOTR) are at an increased risk of developing cSCCs due to immunosuppression/modulation from the necessary regimen to minimize risk of transplant rejection. Studies have found the use of oral sirolimus has reduced the risk of developing cSCC but can also lead to adverse effects such as diarrhea, peripheral edema, rash, mouth ulcers, acne, and pneumonitis.

This study was a 12-week randomized, double-blind, vehicle-controlled pilot study comparing once-daily topical sirolimus gel on the dorsal hand and forearm vs. vehicle on the contralateral hand/forearm to determine the effect on incidence of cSCC in patients with a history (≥5 NMSCs over 5 years and ≥5 “keratocytic lesions” on dorsal hands and forearms) of NMSCs.

The authors found that among 29 patients (mean age of 61.8 years) that were enrolled in the study, the number of keratocytic lesions was reduced by ~31% (p=.0001) on the treated side but increased on the contralateral hand/forearm that received a vehicle gel. Patients received follow-up over 25.5 month and were found to have a 81% decrease in intraepithelial carcinomas on the treated side vs. non-treated side, but no difference in number of cSCC (p=.25). 38% discontinued the study early due to: convenience (n=5), unrelated adverse events (n=5), contact dermatitis (n=1) after ~5 weeks of topical sirolimus use.

Limitations of the study include small sample size, especially since only 18 patients completed the 12 week study. Furthermore, given the chronic nature of both immunosuppression for SOTR and actinic damage/skin cancer, longer term treatment and outcomes are also necessary. Ultimately this study provides initial insight to topical immunosuppression and management of field cancerization and may encourage additional studies for the management of NMSCs.