Cutting-edge experimental therapies are showing promise in clinical trials as nonsurgical alternatives for the treatment of advanced basal cell carcinoma (BCC) and actinic keratosis (AK), says Ellen S. Marmur, M.D., who spoke at the 2010 joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology & Aesthetic Surgery.
Chicago - Cutting-edge experimental therapies are showing promise in clinical trials as nonsurgical alternatives for the treatment of advanced basal cell carcinoma (BCC) and actinic keratosis (AK), says Ellen S. Marmur, M.D., who spoke at the 2010 joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology & Aesthetic Surgery.
A phase 1 study to assess the safety, pharmacokinetics and biological activity of GDC-0449 enrolled 33 patients with metastastic or locally advanced BCC. The study had a dose-ranging design - 17 patients received 150 mg once daily, 15 patients were treated with a dose of 270 mg once daily and one patient received 540 mg once daily. Eligible patients were age 18 and older with histologically confirmed disease considered to be refractory to surgery or radiotherapy.
After an average treatment time of 9.8 months, 18 (54.5 percent) of the 33 patients had some objective response based on imaging and/or physical examination. The response was complete in two (6 percent) patients and partial in 16. The disease remained stable in 11 patients and progressed in four.
"Disease stabilization is potentially an acceptable treatment outcome for patients with advanced BCC," Dr. Marmur says.
Adverse events reported in the study included fatigue (12 percent), hyponatremia (6 percent), muscle spasms (3 percent) and atrial fibrillation (3 percent). Based on the antitumor activity demonstrated in the phase 1 study and the acceptable safety profile, a phase 2 trial of GDC-0449 treatment for advanced BCC was launched, recruiting 100 patients who would receive a dose of 150 mg daily until either study completion, the development of intolerable toxicity or progression of disease. Dr. Marmur is participating as a clinical investigator in this multicenter international study.1
Topical AK treatment
Ingenol mebutate (Peplin), formerly known as PEP005, is being investigated as a topical gel for the treatment of AKs. Derived from the sap of a medicinal plant, euphorbia peplus, ingenol mebutate is a toxic irritant and has been shown in in vitro and animal studies to inhibit the survival of various tumor cell lines, including human melanoma, prostate and breast cancer.
"In the animal studies, the growth inhibitory effects of topical ingenol mebutate were evident even after a very short, one-hour application time," Dr. Marmur says.2-4 Separate multicenter, randomized, vehicle-controlled phase 3 studies enrolling patients with multiple AKs on the head (face or scalp) or nonhead locations have been completed. Dr. Marmur was an investigator in the head AK study, during which patients applied vehicle or ingenol mebutate 0.015 percent gel at bedtime for three consecutive nights. The gel was kept on overnight and washed off after eight hours. The data is not yet published.
Safety data from the phase 2 studies (ref) showed that the drug has very limited transcutaneous penetration, but it does cause significant irritation. Patients generally develop mild erythema after the first night of use that becomes more moderate in severity by day four and begins to resolve gradually at about day eight. At day 29 of follow-up, the treated sites are well healed.5-7