title: Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor.
abstract: The Ras-Raf-MEK-ERK signalling pathway is frequently dysregulated in human malignancies, as is angiogenesis and the vascular endothelial growth factor receptor (VEGF/VEGFR) pathway. These kinases are therefore important anticancer targets. The novel, oral treatment sorafenib (BAY 43-9006), has been shown to be an inhibitor of VEGFR, Raf and platelet-derived growth factor in clinical trials against a variety of cancers, with the greatest activity to date observed in metastatic renal cancer. Although side-effects with this targeted therapy are usually not dose-limiting, they frequently involve the skin, and consist of a maculopapular rash, palmar-plantar dysaesthesia, alopecia and xerosis. In this report, we present two patients in whom treatment with sorafenib resulted in inflammation of actinic keratosis, which in some cases progressed to invasive squamous cell carcinoma. This side-effect is of clinical importance, as early recognition is critical for early treatment and may represent a source of additional morbidity to these patients.
authors.affiliation: Section of Dermatology, Department of Medicine, University of Chicago, IL, USA. m-lacouture@northwestern.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Lacouture
authors.forename: A
authors.initials: A
authors.lastname: Desai
authors.forename: K
authors.initials: K
authors.lastname: Soltani
authors.forename: V
authors.initials: V
authors.lastname: Petronic-Rosic
authors.forename: A E
authors.initials: AE
authors.lastname: Laumann
authors.forename: M J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: W M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects; D001557:Benzenesulfonates / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007642:Keratosis / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010787:Photosensitivity Disorders / Q000139:chemically induced* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib