Topical treatment alone insufficient for many NMSCs

New York - Except in limited instances, an expert says, topical therapies for medical management of nonmelanoma skin cancers (NMSCs) work best as adjuncts to surgery.

As monotherapy, says Fiona O’Reilly Zwald, M.D., “I typically use topical agents (off-label) for AKs, superficial basal cell carcinomas (BCCs) and perhaps squamous cell carcinoma (SCCs) in situ. However, I would not use topical agents for more invasive SCC or nodular BCC. That’s where surgery is needed.” Dr. Zwald is a Mohs surgeon based in metro Atlanta whose practice revolves around the care of high-risk skin cancers associated with organ transplant recipients.

Only when a patient is not a surgical candidate should dermatologists consider topical treatment alone for more aggressive skin cancer, Dr. Zwald says.

“Treatment of field disease is another area that’s very important for preventing the progression of skin cancer,” she says. Topical agents can provide benefits here because they can be used over wide body surface areas.

As adjunctive therapies, Dr. Zwald says, topical agents can be used before or after surgical removal of skin cancers. Overall, topical agents “will probably help to clear the skin in many instances. But they’re not supposed to be used as a replacement for surgery,” she notes.

Eye on immunosuppression

When treating immunosuppressed patients such as those who have received organ transplants, Dr. Zwald says, “I’ll often treat them surgically, while also having them on a regimen of topical therapies.” Using topical agents presurgically can reduce the need for more invasive treatments, and the attendant potential for scarring, she says.

“I tell patients that if any lesion pops through while they’re on the topical regimen, they need to get biopsied,” Dr. Zwald says.

As for specific topical treatments, “Efudex (5-fluorouracil/5-FU, Valeant) and Aldara (imiquimod, Medicis/Valeant) are the major agents we've used for many years now,” she says. Patients typically must apply these drugs daily for six to eight weeks to see results.

Dermatologists also may use 5-FU in the form of chemo wraps, she says.

“We clean the skin, then apply 5-FU directly on the area being treated, and wrap the skin with Kerlix (Covidien) gauze embedded in a zinc oxide paste,” Dr. Zwald says. After applying a layer of petroleum jelly over this layer, another layer of Kerlix follows, and then an outer layer of Coban (3M). Patients leave the wrap on for a week before returning to the office.

Additionally, Dr. Zwald says she occasionally prescribes oral 5-FU (capecitabine) - usually in conjunction with a medical oncologist, who checks the patient’s kidney and liver functions before treatment and monitors these functions during treatment. “Because it’s hard to tolerate, we use it only for who don’t have other options. Some patients do very well on it,” she says.

Capecitabine causes very strong inflammatory reactions, according to Dr. Zwald.

“Patients also experience significant desquamation on the hands and feet,” which helps to reduce actinic keratoses (AKs) and pre-skin cancers, she says. A typical regimen consists of four weeks on therapy, alternating with four weeks off.

Trying PDT and topical gels

Topical therapies gaining increased attention include photodynamic therapy (PDT) and Picato gel (ingenol mebutate, Leo). Unlike 5-FU and imiquimod, Dr. Zwald says, ingenol mebutate only requires application for two to three days. A prospective study has shown that around 57 days later, “There is a complete response rate of around 42 percent in patients who have had it used on the face, scalp, trunk and extremities (Lebwohl M, Swanson N, Anderson LL, et al. N Engl J Med. 2012;366(11):1010-1019).”

In a recent study, patients applied ingenol mebutate gel to skin cancers of the face and scalp for three days, or cancers of the trunk and extremities for two days. At 12 months post-treatment, 87 percent of patients with cancers of the face and scalp remained completely cured, as did 86 percent with cancers of the trunk and extremities (Lebwohl M, Shumack S, Stein Gold L, et al. JAMA Dermatol. 2013;149(6):666-670).

Drawbacks of topical agents include patient compliance and persistence, she says. For example, “Ingenol mebutate causes a tremendous local skin reaction. But it is efficacious. So the more reaction a patient gets, the better the outcome. Not every patient can go through that,” Dr. Zwald says.

Somewhat similarly, she says, PDT causes a sunburn-like reaction that desquamates superficial skin layers.

“If patients forget to apply sunblock after PDT, they’re going to have a pretty extensive reaction,” she says. Accordingly, Dr. Zwald says that any nonsurgical therapy requires thorough patient education, particularly regarding how to protect treated skin from the sun, and which lesions require evaluation by a dermatologist.

Disclosures: Dr. Zwald reports no relevant financial interests.