Does Basal Cell Carcinoma Belong to the Spectrum of Sorafenib-Induced Epithelial Skin Cancers?

Abstract

The multikinase inhibitor sorafenib is therapeutically used in various malignancies. Multiple cutaneous side effects are well described but recent reports indicated a possible association of epithelial skin cancer growth during sorafenib therapy. To our knowledge, few cases of actinic keratoses and variants of squamous cell carcinomas associated with sorafenib have been published. We report 2 patients who developed a basal cell carcinoma (BCC) while treated with sorafenib. Interestingly BCC is a tumor which has not been described yet in association with sorafenib therapy. The tumors were excised completely. After termination of sorafenib treatment, no new BCCs or other epithelial skin cancers occurred. There is accumulating evidence in the literature that sorafenib and possibly other targeted agents are associated with an increased occurrence of epithelial skin cancers. These observations are summarized here and complemented by the new observation that al- so BCCs might be associated with sorafenib therapy. The pathogenetic mechanisms are unclear so far but induction of the mitogen-activated protein kinase pathway in wild-type RAF cells by RAF inhibitors might play a role. Patients should be informed of this possible side effect and undergo regular dermatological controls before and during sorafenib therapy.

Skin Cancer Associated With the Use of Sorafenib and Sunitinib for Renal Cell Carcinoma

“…The largest case series on this topic (Table ) did not report the observation of BCC in patients with RCC treated with sorafenib. One other recent publication reported on the development of BCC in two patients, each while treated with sorafenib . We noted the appearance of BCC in one patient treated with sorafenib and two with sunitinib.…”

“…Shortly after FDA approval of sorafenib for the treatment of RCC, some case reports appeared of patients developing squamous cell carcinomas (SCC), keratoacanthomas (KA), and inflammatory actinic keratoses (AK) . More recently, several case series have described patients developing SCC, basal cell carcinoma (BCC), and KA within a few months of starting therapy with sorafenib …”

Raf kinases in cancer–roles and therapeutic opportunities

“…The underlying mechanism is an allosteric effect of the drug, which enforces the dimerization of endogenous BRAF with CRAF or ARAF (Hatzivassiliou et al, 2010;Heidorn et al, 2010;Poulikakos et al, 2010). Within these dimers, only one active component is required for activation of the MEK-ERK pathway; therefore, at non-saturating concentrations, the inhibitors activate the pathway rather than disabling it, particularly in the presence of activated RAS, and it is possible that the rapid development of benign skin tumors in patients treated with RAF inhibitors might be fueled by such a mechanism (Degen et al, 2010;Robert et al, 2010) (Figure 4).…”

Central Upper Lip Reconstruction by Two Vermillion Flaps and a Rotational Skin Flap

“…Skin type, cumulative lifetime sun exposure and sporadic exposure to ultraviolet radiation are known risk factors for developing BCC. Moreover, recent reports have shown a possible risk of developing BCCs during sorafenib therapy [2]. …”