PALM BEACH, FLA. Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.
The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.
"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.
Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.
"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.
The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.
"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.
The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.
After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.
"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."
The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.
Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.
The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.
"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.