WAILEA, HAWAII – The search is on for new topical therapies for actinic keratoses (AKs) that patients will find more appealing than what’s now available, according to Neal Bhatia, MD.
Compliance with current topical field agents for actinic keratoses is not great. Many patients balk at the intense local skin reactions these agents elicit. There is a misplaced sense, especially among patients who don’t grasp the relationship between AKs and squamous cell carcinoma, that the treatment is worse than the disease, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
One that he said he is particularly excited about is a novel formulation of 4% 5-fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil. In a recently published, double-blind, multicenter clinical trial involving 841 patients, once-daily application of this product for 4 weeks provided better outcomes and superior tolerability, compared with the old-school regimen of 5% 5-FU cream twice daily.
One hundred percent of patients on 4% 5-FU in peanut oil achieved at least 75% clearance of AKs, as did 95% of those on twice daily 5% 5-FU. The incidence of application site skin irritation in the group on the novel product was only 30%, compared with 60% in the comparison group ().
The peanut oil provided a moisturizing effect and was safe even in patients with peanut allergy, Dr. Bhatia noted.
Another product in development as a topical field therapy for AKs is ingenol disoxate gel, a relative of ingenol mebutate (Picato). Unlike ingenol mebutate, ingenol disoxate remains stable without refrigeration. It’s also a more potent activator of protein kinase C. In mouse models, it shows significantly more cytotoxic potency than does ingenol mebutate.
Based upon the favorable results of a short-term, double-blind phase II study, Leo Pharma now has ingenol disoxate in larger clinical trials as field therapy for AKs on the full face, scalp, or chest, with treatment of larger surface areas than those for which ingenol mebutate is approved ().
Actikerall is also in the developmental pipeline. It consists of 0.5% 5-FU, in combination with 10% salicylic acid, in a film-forming base. Developed by Almirall, it is marketed in Canada by Cipher Pharmaceuticals.
SR-T100 gel utilizes as its active ingredient an antiproliferative extract of Solanum lycocarpum, the Brazilian wolf apple. Taiwan-based G & E Herbal Biotechnology is developing the product, which is in an ongoing phase II clinical trial.
Other novel agents for topical field therapy in phase II studies are KX2-391 ointment, a dual Src kinase/tubulin polymerization inhibitor that causes apoptosis of hyperproliferating cells, under development by Athenex, and Vidac Pharma’s VDA-1102 ointment, which selectively triggers apoptosis in neoplastic cells by modulating voltage-dependent anion channel 1/hexokinase enzyme 2, with minimal impact upon surrounding normal cells.
The principle underlying topical field therapy, compared with simply freezing AKs once they arise, is straightforward, Dr. Bhatia stressed. “It’s the difference between treating only what we can see and treating what’s also on the way.”
Dr. Bhatia reported having financial relationships with more than two dozen pharmaceutical companies. SDEF and this news organization are owned by the same parent company.