Invasive Squamous Cell Carcinoma and Sorafenib in a Black Patient

To the Editor: Sorafenib, which interrupts oncogenic pathways by inhibiting tyrosine, serine and threonine kinases, is approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. This multikinase inhibitor has also been used for treating patients with other solid tumors.1,2 Recent reports in the Archives of Dermatology have emphasized the development of squamous cell carcinomas in sorafenib- treated cancer patients: multiple squamous cell carcinomas localized to the lower extremity treated with melphalan isolated limb infusion in a white man with metastatic melanoma of that limb3 and squamous cell carcinoma on the non-sun exposed hip of a black man with unresectable hepatocellular carcinoma.4 Earlier studies have not only observed the appearance of squamous cell carcinomas, but also keratoacanthomas and actinic keratoses in oncology patients after initiating treatment with sorafenib.1,2 The development of premalignant and malignant skin lesions in patients receiving sorafenib adds new insight into the potential pathogenesis of nonmelanoma skin cancer and raises important issues regarding the management of sorafenib-treated individuals in whom these tumors occur. The lesions most commonly appear in white men with no prior history of skin cancer who are more than 40 years old. They appear as soon as 2 weeks and as late as 3 years after starting sorafenib treatment.2
The observation by Raymond et al suggests that prior and concurrent melphalan isolated limb perfusion to the affected extremity promoted the development of a local cutaneous immunocompromised "district";5 3 squamous cell carcinomas developed within 11 weeks after initiation of sorafenib.3 The report by Donaldson et al shows that all skin types are susceptible to sorafenib-related squamous cell carcinomas and that some of the previously associated etiologic factors, such as light skin color and sun exposure, may not have a significant role in the pathogenesis of nonmelanoma skin cancer in these individuals.4 And, the recent observation of not only squamous cell carcinoma, but also verruca vulgaris and actinic keratosis with features of verruca vulgaris in a 77-year-old white man with metastatic adenocarcinoma of the lung (and a prior history of nonmelanoma skin cancers) within 1 month after starting sorafenib (400 mg twice daily) raises the possibility that human papillomavirus may be associated with the pathogenesis of squamous cell carcinoma in some of these individuals.2
Definitive guidelines for the management of oncology patients with sorafenib-associated squamous cell carcinomas or keratoacanthomas remain to be established. It is reasonable to consider briefly stopping the agent while treating the skin tumor. Thereafter, especially in patients whose primary malignancy is responding to treatment, there is no absolute contraindication to continuing sorafenib therapy. However, the patient should be examined regularly with diligent surveillance for new cutaneous tumors.2
References
1. Hong DS, Reddy SB, Prieto VG, Wright JJ, Tannir NM, Cohen PR, Diwan AH, Evans HL, Kurzrock R: Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib. Arch Dermatol 2008;144:779-782.
2. Williams VL, Cohen PR, Stewart DJ: Sorafenib-induced premalignant and malignant skin lesions. Int J Dermatol, in press.
3. Raymond AK, Puri PK, Selim MA, Tyler DS, Nelson KC: Regional squamous cell carcinomas following systemic sorafenib therapy and isolated limb infusion for regionally advanced metastatic melanoma of the limb. Arch Dermatol 2010;146:1438-1439.
4. Donaldson MR, Stetson CL, Smith JL: Invasive squamous cell carcinoma and sorafenib in a black patient. Arch Dermatol 2011;147:133-134.
5. Chodkiewicz HM, Cohen PR: Radiation port erythema multiforme: erythema multiforme localized to the radiation port in a patient with non small cell cancer. SkinMed, in press.

Conflict of Interest: None declared