Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib

Arch Dermatol. 2008 Jun;144(6):779-82. doi: 10.1001/archderm.144.6.779.


Background: Keratoacanthomas, as well as an actinic keratosis progressing to squamous cell cancer, have been reported in patients who were treated with sorafenib, a multikinase inhibitor known to suppress the actions of Raf kinase and vascular endothelial growth factor receptor.

Observations: We describe a 70-year-old white woman with metastatic renal cell carcinoma who was treated with a combination of sorafenib and tipifarnib (a farnesyltransferase inhibitor). She had no history of skin cancer. However, within 3 months after starting this therapy, she developed 3 erythematous nodules on her legs. Pathologic examination showed deeply invasive, well-differentiated squamous cell carcinomas. The tumors were excised, and sorafenib-tipifarnib treatment was discontinued. No new lesions have developed to date.

Conclusions: Targeted agents, such as sorafenib and tipifarnib, are increasingly being used in the management of visceral malignant neoplasms. A temporal relationship was observed between the initiation of the targeted treatments and the emergence of these cutaneous cancers. Further study of the mechanisms responsible for the rapid appearance of squamous cell cancers in this setting may provide insights into the pathogenesis of skin tumors.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Benzenesulfonates / adverse effects*
  • Benzenesulfonates / therapeutic use
  • Biopsy
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Squamous Cell / chemically induced*
  • Carcinoma, Squamous Cell / pathology
  • Diagnosis, Differential
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / secondary
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Quinolones / adverse effects*
  • Quinolones / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / pathology
  • Sorafenib


  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Quinolones
  • Niacinamide
  • Sorafenib
  • Receptors, Vascular Endothelial Growth Factor
  • tipifarnib