New options available in cutaneous oncology

Fiona O'Reilly Zwald, MD

Fiona O’Reilly Zwald, MD: “We need options beyond surgery to help us manage these patients.”

Treatment options for cutaneous cancers are advancing rapidly, and some of them were developed specifically for dermal applications while others were pioneered in noncutaneous settings. Some treatments are well supported with clinical trial data and others rely largely on retrospective studies.

“Transplant recipients get very aggressive forms of skin cancers,” said Fiona O’Reilly Zwald, MD, “While I do a lot of surgery for these patients, I’m always looking for nonsurgical options. We need options beyond surgery to help us manage these patients.”

Dr. Zwald directed “Update Platform: Cutaneous Oncology” (S003) on Aug. 7 and reviewed the latest treatment options for organ transplant patients. Organ transplantation patients are a unique population because they are immunosuppressed. Immunosuppression protects their engrafted organs but also makes them more susceptible to cutaneous cancers.

Surgery is the standard treatment for skin cancers in organ transplant patients, but surgery can be inadequate for deeply invasive tumors. The latest nonsurgical options include endothelial growth factor receptor (EGFR) inhibitors, novel treatment protocols using familiar topical agents, and photodynamic therapy.

“EGFR inhibitors have been studied extensively in the head and neck literature, but their use in transplant patients is still being investigated,” Dr. Zwald said. “A lot of the data are based on retrospective studies of two to five years. The picture is similar in photodynamic therapy. Incubation timing and protocols have been studied intensively in nonimmunosuppressed patients, but in the immunosuppressed world of organ transplantation, we are just starting to look at these agents and treatments in the last few years.”

The clinical data are stronger when it comes to new agents for patients who are not immunocompromised. One of the newest is vismodegib, an inhibitor of the vascular endothelial growth factor (VEGF) pathway. The agent has been shown to reduce the size of large basal cell carcinomas that are not amenable to surgical therapy.

0814-Update Platform

(From left) Fiona O’Reilly Zwald, MD; Michel McDonald, MD; Sarah Myers, MD; Scott Fosko, MD

Scott Fosko, MD, professor and chair of dermatology at St. Louis University School of Medicine, discussed the data for and against the use of vismodegib in nevoid basal cell carcinoma syndrome and other cutaneous tumors.

“This drug has wonderful indications, but how often do patients present with morbid basal cell carcinomas that you can’t operate on outside the realm of nevoid basal cell carcinoma syndrome?” Dr. Zwald asked. “This drug may be an adjuvant to surgical therapy for a small percentage of the patient population.”

Michel McDonald, MD, director of dermatologic surgery and associate professor of medicine at Vanderbilt University, Nashville, Tennessee, explored the latest options in topical treatments for skin cancer. Clinicians can choose from new formulations and treatment protocols for familiar agents such as 5-FU (fluorouracil) and imiquimod that are designed to reduce toxicities, thereby improving compliance and clearance rates. Or they can use the newest topical, ingenol mebutate.

“The wonderful thing about this agent is that you can use it for two or three days in a patient with extensive actinic keratosis damage with good long-term clearance rates,” Dr. Zwald said. “Compare that with imiquimod or 5-FU where the patient could be on treatment for eight weeks or longer. Ingenol causes a lot of skin irritation, just like the other alternatives, but one course is completed after three applications. That can make a tremendous difference in compliance and outcome.”

Sarah Myers, MD, associate professor of dermatology at Duke University School of Medicine, Durham, North Carolina, presented the latest findings on the use of EGFR inhibitors such as cetuximab, gefitinib, and erlotinib. EGFR inhibitors have a long history of use in cancers of the lung, anus, head, neck, and other tissues. There also are positive data for use in squamous cell carcinoma.

“These agents prevent cancer cells from replicating so the tumor does not continue to proliferate,” Dr. Zwald said. “Cetuximab is the best known, while gefitinib and erlotinib are second-generation agents that seem to have a better response rate. If patients are EGFR-positive, you get about a 60 percent response rate, which is much better than with conventional chemotherapy. There are still a lot of questions, but EGFR inhibitors are one more option for aggressive squamous cell carcinoma in high-risk patients.”

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