Cancer management: Research suggests a growing role for medical therapy for NMSCs

Key Points

"Combination therapy is used routinely in the management of many types of solid tumors where radiation or surgery is performed first as a definitive treatment or to reduce the tumor burden, and then adjuvant treatment is used to clear residual tumor and prevent recurrence.

"Therefore, we must ask why this approach is not being used more often in treating skin cancers," Dr. Bhatia says.

Of particular interest, a published study on imiquimod treatment of biopsy-confirmed superficial basal cell carcinoma (sBCC) reported data from five years of follow-up, Dr. Bhatia says (Gollnick H, Barona CG, Frank RGJ, et al. Eur J Dermatol. 2008; 18(6): 1-6).

Results from this multicenter European study showed that 90 percent of 182 treated patients achieved clearance with initial treatment that consisted of imiquimod application five times a week for six weeks. Sustained clearance rates at three, four and five years were 91, 90, and 87 percent, respectively.

"These long-term data provide some added reassurance about using imiquimod for primary management of sBCC, because they indicate to me I probably don't have to worry too much about recurrence in successfully treated patients being lost to follow-up," Dr. Bhatia explains.

Oral retinoids

Oral retinoids have an important role as chemopreventive agents in patients at high risk for NMSC, although there may be some reluctance to prescribe acitretin or isotretinoin due to concerns about safety and tolerability.

To improve tolerability, safety and compliance, chemoprevention with oral retinoids should be initiated with a low dose (e.g., acitretin 10 mg QOD) that is titrated up.

For monitoring, Dr. Bhatia says he only checks serum lipids and performs bone mineral density measurements to screen for osteoporosis in women. Encouraging weight control among patients is also helpful to avoid retinoid-induced lipid elevations.

Systemic therapy

Aside from oral retinoids, celecoxib is being investigated as a systemic therapy for NMSC chemoprevention.

Interest in this inhibitor of cyclooxygenase-2 (COX-2) relates in part to the finding that COX-2 expression is increased in UV-exposed skin and results in high levels of prostaglandin E, which can be tumorigenic. Efficacy for decreasing photocarcinogenesis was previously demonstrated in a mouse model.

The investigational agent T4 endonuclease 5 (T4N5) liposomal lotion is being studied as a topical agent for NMSC chemoprevention. T4N5 is a bacterial DNA repair enzyme and has been associated with encouraging results for decreasing the development of actinic keratoses and NMSCs in normal individuals and patients with xeroderma pigmentosa.

Topical agents

Available topical products that are being evaluated as primary treatment for existing tumors include topical tazarotene 0.1 percent gel (Tazorac, Allergan) and sinecatechins 15 percent (Veregen, MediGene).

Published data from a study evaluating tazarotene treatment of sBCC showed a 60 percent clearance rate for head and neck lesions and lower efficacy at other anatomic sites.

"These outcomes were achieved after 24 weeks of application. Perhaps tazarotene is better as an adjunct applied to areas of photodamage to provide a field effect in patients who have been treated for sBCC," Dr. Bhatia says.

Sinecatechins are an extract of green tea and have been reported to have multiple activities that would suggest a benefit for cancer treatment.

Research shows they inhibit major functions of the human papilloma virus and tumor cell growth as well as stimulate the immune system. There is also evidence to suggest they have antioxidant activity, induce apoptosis, and reduce the potential for angiogenesis, Dr. Bhatia says.

Studies of NMSC treatment with ingenol mebutate gel (Peplin) in the United States are also under way or have been completed. So far, some promising data have emerged from studies in Australia that enrolled patients with actinic keratoses and superficial and nodular BCC.

Results in those trials showed 40 percent of lesions treated with ingenol mebutate were almost or completely cleared compared with only 15 percent of placebo-treated controls.

Disclosures: Dr. Bhatia is a consultant to Graceway, Ortho-Neutrogena, Quinnova and Stiefel.