This is an interesting review of some newer non-surgical techniques.
Let me know what you think.
There are innovations in nonsurgical modalities for the treatment of actinic keratoses (AKs) and nonmelanoma skin cancers (NMSCs) and a basis for broadening the use of preventive strategies, says Leonard H. Goldberg, M.D. “Surgical excision remains the gold standard for treating basal cell and squamous cell carcinomas, but we now have alternatives offering cure rates approaching those achieved with surgery,” says Dr. Goldberg, who is in private practice, DermSurgery Associates, Houston, and clinical professor of dermatology, The Methodist Hospital, Weill Medical College, Houston.
“Oral compounds in clinical development are producing exciting results, and we recognize that our nonsurgical modalities represent a valuable approach to providing field-directed prophylaxis,” he says.
Oral acitretin (Soriatane, Roche) has a long history of use as NMSC chemoprophylaxis in organ transplant recipients and other immunosuppressed patients. However, Dr. Goldberg also believes all immunocompetent patients who have had a NMSC or multiple AKs on the face or scalp should be offered the option of routine, field-directed prophylaxis using topical chemoprevention with 5-fluorouracil (Efudex, Valeant; Carac, Sanofi-Aventis) or diclofenac (Solaraze, PharmaDerm), topical immunotherapy (Aldara, Zyclara; Graceway) or photodynamic therapy (PDT).
In his practice, patients who have been treated for AKs are asked to return for follow-up after six months and are retreated as needed. Patients who develop recurrent lesions are scheduled for prophylactic treatment every six months while others are treated on an annual schedule. Chemoprevention agents may be rotated at successive treatment intervals, particularly in patients who develop new lesions, in order to take advantage of the different mechanisms of action.
For primary treatment of AKs, the efficacy and safety of cryotherapy are improved with the use of a newer liquid nitrogen dispenser (Cry-Ac Tracker, Brymill) featuring an integrated infrared sensor that enables temperature-controlled treatment, Dr. Goldberg says.
The sensor measures skin surface temperature and, using a three-color-coded light system, provides a visual indication to the operator when the desired skin temperature is reached. The system is able to guide freezing of the epidermis and upper dermis to -5 degrees Celsius, which is adequate for AK clearance. This will avoid destruction of deeper tissue and therefore the development of scarring and hypopigmentation, Dr. Goldberg says.
“Cryosurgery remains the treatment of choice for individual AKs because it achieves high rates of clearance. However, the response can be unpredictable due to variability in treatment delivery. As reported in several published studies, average clearance rates for AKs are only about 75 percent,” he says.
A recently published study by Dr. Goldberg and colleagues demonstrated the efficacy and safety of the new cryotherapy unit (Dermatol Surg. 2010;36(12):1956-1961). It included 36 patients with Fitzpatrick skin types I-III who had a total of 180 thin AKs treated using a circular, painting method with a wide freeze. All lesions were marked at baseline and photographed. At follow-up at six weeks, 100 percent clearance was achieved, and patients were satisfied with the results.
At one week post-treatment, erythema (42 percent) and crusting (21 percent) were the most common complications seen; oozing and ulceration each occurred at rates of 3 percent. All skin-related adverse events had resolved completely by six weeks and there were no cases of AK recurrence, scarring or hypopigmentation, Dr. Goldberg says.
The oral Hedgehog signaling pathway inhibitor GDC-0449 (Vismodegib, (Genentech/Curis) is currently being evaluated in phase 2 clinical trials for the treatment of basal cell nevus syndrome (BCNS) and sporadic basal cell carcinomas (BCCs). Based on his experience as an investigator in a clinical study of GDC-0449, Dr. Goldberg says he considers it to be an absolute miracle drug for BCNS, and he believes it also has the potential to change the treatment paradigm for BCC in the future.
Dr. Goldberg has published on the efficacy of GDC-0449 for treating BCNS-associated BCCs and odontogenic keratocysts of the jaw (Arch Dermatol. 2010;146(1):17-19; Arch Dermatol. 2011;Mar 21 Epub ahead of print).
“GDC-0449 has shown itself to be well-tolerated and a life-altering drug for BCNS patients, and I believe it is the long-sought after silver bullet for this condition because it frees patients from frequent, mutilating surgery,” he says.
Capecitabine (Xeloda, Hoffman-LaRoche), an oral nucleoside metabolic inhibitor with antineoplastic activity approved for use in treatment of colon, colorectal and breast cancer, is also being investigated for the treatment of advanced squamous cell carcinoma.
Capecitabine is a prodrug that is enzymatically converted to 5-fluorouracil selectively within tumor cells and has shown promise alone and when combined with subcutaneous interferon alpha in patients with advanced cutaneous squamous cell carcinoma (Wollina U, Hansel G, Koch A, et al. J Cancer Res Clin Oncol. 2005;131(5):300-304). It is useful for reducing new lesion development in organ transplant recipients with a history of recurrent NMSCs (J Clin Oncol. 29;27:1519).
As a downside, its side effect profile in these early studies included relatively high rates of grade 3/4 fatigue, hand-foot-syndrome and diarrhea.
Although nonablative fractional laser resurfacing with a 1,550 nm proprietary device (Fraxel re:store, Solta Medical) has been approved for treatment of AKs, it was found to be ineffective in a histologically controlled study conducted by Dr. Goldberg and colleagues (J Am Acad Dermatol. in press). The study included 14 patients who underwent five laser treatments at two- to four-week intervals using a fluence of 20 mJ to 7 mJ, treatment level of 11, 32 to 40 percent surface area coverage, and eight to 10 passes. Lesions were counted and photographed at baseline, before each treatment and at one, three and six months after the last treatment, and biopsies were obtained at baseline and at the three-month follow-up.
The clinical efficacy assessment showed the lesion clearance rate decreased as follow-up lengthened. At one month, there was an almost 75 percent reduction from baseline lesion count, but by six months only half of the AKs remained cleared, and the post-treatment biopsies documented lesion persistence.
“The fractional laser treatment coagulates epidermal and dermal tissue up to a depth of 140 microns. However, it only ablates small microzones, and clearance of AKs requires total ablation of the involved skin. Clearance of this device for treatment of AKs was based on demonstration of its clinical efficacy and safety, but there was no requirement of proof based on pathological evaluation,” Dr. Goldberg says.