SAN DIEGO – Sorafenib, an oral agent used to treat advanced kidney cancer and unresectable liver cancer, works like "fertilizer" for lesions resembling keratoacanthomas, producing a multitude of the horny epithelial tumors in oncology patients, according to Dr. Ronald P. Rapini.
Marketed as Nexavar by Onyx Pharmaceuticals and Bayer HealthCare, sorafenib is one of many new protein kinase inhibitors approved and in development for the treatment of various forms of cancer, including leukemia.
Courtesy Dr. Ronald Rapini
Multiple keratoacanthomas in a patient taking sorafenib.
The agents have been called "smart drugs" for their ability to mediate signaling pathways that underlie many functions of malignant cells, including growth, differentiation, and apoptosis.
"You will see this," Dr. Rapini said at a meeting sponsored by the American Society for Mohs Surgery. Medical oncologists "are using these [drugs] like crazy."
Other examples of protein kinase inhibitors are imatinib, a tyrosine-kinase inhibitor (TKI) marketed by Novartis as Gleevec, for chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs), and sunitinib, marketed by Pfizer as Sutent, for GISTs, advanced kidney cancer, and pancreatic neuroendocrine tumors, noted Dr. Rapini, professor and chair of dermatology at the University of Texas Health Science Center and M.D. Anderson Cancer Center in Houston.
No keratoacanthomatous lesions have been reported to date with bosutinib, a third-generation TKI under investigation by Pfizer for the treatment of various forms of cancer, including leukemia, he said.
The initiation of benign tumor growth is likely secondary to the multikinase inhibitor mechanism of action of the oncologic drugs.
Management of the keratoacanthomalike lesions is not clear; Dr. Rapini said the role of retinoids in such cases is "questionable," with "believers and nonbelievers."
The lesions may regress upon discontinuation of the protein kinase inhibitor; otherwise, they "relentlessly" continue to develop.
Other reported skin reactions seen in conjunction with protein kinase inhibitor therapy include skin rashes, pruritus, blistering, peeling skin, hand-foot skin reaction, and difficulties with wound healing.
Dr. Rapini said he had no relevant financial disclosures.