Topical 5-Fluorouracil Elicits Regressions of BRAF Inhibitor–Induced Cutaneous Squamous Cell Carcinoma

Abstract

The protein kinase BRAF regulates cell growth through the mitogen-activated protein kinase (MAPK) pathway. In about half of the melanomas, BRAF is mutated and acts as a driver oncogene that stimulates cell proliferation, survival, and tumor progression (Davies et al., 2002; Gray-Schopfer et al., 2007). The anti-BRAF drugs vemurafenib (PLX4032/RG7204) and dabrafenib (GSK2118436) achieve objective clinical responses in about 60% of melanoma patients whose tumors express mutant BRAF (Flaherty et al., 2010; Chapman et al., 2011; Sosman et al., 2012), validating these drugs as a

BRAF inhibitor-associated cutaneous squamous cell carcinoma: new mechanistic insight, emerging evidence for viral involvement and perspectives on clinical management

“…The nucleotide analogue and antimetabolite, 5‐fluorouracil, has been identified as another potential alternative to surgical excision. Regression of BRAF inhibitor‐induced cSCCs was observed in a number of patients receiving 5‐fluorouracil in the form of a topical cream . The rate of cSCC recurrence on follow‐up examination at 11 or 18 months was minimal, and significant adverse reactions to treatment have not been reported .…”

“…Regression of BRAF inhibitor‐induced cSCCs was observed in a number of patients receiving 5‐fluorouracil in the form of a topical cream . The rate of cSCC recurrence on follow‐up examination at 11 or 18 months was minimal, and significant adverse reactions to treatment have not been reported . In addition, inhibition of the cyclooxygenase‐2 pathway has been shown to prevent the development of BRAF inhibitor‐associated cSCCs in mouse models.…”

Management of the Cutaneous Adverse Effects of Antimelanoma Therapy

“…This is especially useful when patients have had an eruption of multiple lesions, or have lesions affecting cosmetically sensitive areas such as the face and scalp. These topical therapies have been shown to be well tolerated and to minimize cuSCC recurrence on follow-up [16].…”

“…Maculopapular exanthemas can occur in all antimelanoma therapies with varying frequency. In the case of anti-PD-1 therapy and anti-CTLA-4 therapy [16], this eruption appears as an exanthema composed of red erythematous papules coalescing into plaques [31], which develop soon after treatment initiation [16].…”

Clinical resolution of vemurafenib-induced squamous cell carcinoma with topical 5-fluorouracil

“…Viros et al . have demonstrated clinical resolution of cutaneous SCC secondary to dabrafenib therapy (GSK2118436) with topical 5‐FU.…”