title: Cutaneous drug eruptions induced by sorafenib: a case series.
abstract: Sorafenib, an epidermal growth factor receptor inhibitor, is a novel treatment used for malignancies resistant to traditional chemotherapy. Epidermal growth factor receptors (EGFR) are a family of 4 transmembrane tyrosine kinase receptors that, via signal transduction pathways, mediate cell growth, differentiation, and survival. Sorafenib is a targeted drug specifically engineered to inhibit Raf serine/threonine kinases, which are part of the reticular activating system (RAS) oncogene pathway. In addition, in vitro studies have shown sorafenib to be a potent multikinase inhibitor, targeting receptor tyrosine kinases associated with tumor angiogenesis (VEGFR-2, VEGFR-3, and PDGFR-beta) and progression. Initially, approved for use in advanced renal cell carcinoma, sorafenib is being studied for the treatment of other solid tumors at our institution. During the clinical trial, 4 patients were referred to the dermatology clinic for evaluation and treatment of diffuse erythematous eruptions all occurring 8 to 10 days after initiating sorafenib at a dose of 400 mg twice daily. These eruptions occurred in demographically similar patients and displayed similar clinical characteristics and histopathological findings. Clinically, 3 of 4 patients had facial erythema, 3 of 4 had generalized macular erythema, 3 of 4 had widespread follicular-based papular eruption, and 4 of 4 had palmoplantar erythrodysesthesia. Half of the patients had cutaneous eruptions without systemic effects, while the other half had hypersensitivity reactions requiring withdrawal from clinical trial. This is the first case series illustrating drug eruptions induced by sorafenib.
authors.affiliation: University of Chicago, Department of Medicine, Section of Dermatology, Chicago, IL, USA. jessica.maddox@uchospitals.edu
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Maddox
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Kung
authors.forename: Vesna
authors.initials: V
authors.lastname: Petronic-Rosic
authors.forename: Aisha
authors.initials: A
authors.lastname: Sethi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000627:therapeutic use; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib