Journal of Clinical and Aesthetic Dermatology

Updates on Psoriasis & Cutaneou Oncology

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

Issue link:

Contents of this Issue


Page 24 of 43

S25 P r o c e e D i n G s JCAD jOUrnAl Of ClInICAl And AEsthEtIC dErMAtOlOgy september 2017 • volume 10 • number 9 • supplement the sustained lesion reduction rates over baseline were 87.2 percent for face and scalp and 86.8 percent for trunk and extremities, with the estimated median time to recurrence set at 365 days (face/scalp) or 274 days (trunk/extremities). 131 no safety concerns were reported during the follow-up period of 12 months. a pooled analysis of ingenol mebutate gel (0.015% for face/scalp aK and 0.05% for aK on the trunk or extremities) found ingenol mebutate was signifcantly more edective than placebo at clearing aK on the face or scalp (42.2% vs. 3.7%, p<0.001) as well as on the trunk or extremities (34.1% vs. 4.7%, <0.001). 1 32 local skin responses peaked at about Day 4 and diminished to baseline by about Day 29. ingenol mebutate has a dual mechanism of action in the treatment of both melanoma and scc. it acts on epidermal cells causing mitochondrial swelling and disruption of the cell membrane, culminating in apoptosis. 133, 134, 135, 136 this cascade leads to ingenol mebutate's immunostimulatory edects and precipitation of the ingammatory response, 136 namely that it increases t-cell activity, increases dendritic cell activity, activates endothelial cells, including il- 1β and tnf-a, releases cytokines 135 and recruits neutrophils. 134 activated β cells release tumor- specifc antibodies that are then bound to antigen-bearing tumor cells; neutrophil binding to the fc portion of tumor cell-bound antibodies results in the activation and release of reactive oxygen species which, in turn, leads to apoptotic cell death and avoids relapses. 134, 135, 137 low-dose 5-guorouracil (5-fu) 0.5% combined with salicylic acid 10% can be used as a topical treatment for hyperkeratonic aK. in a proof-of-concept study (n=15, 66 aK), treatment occurred three times weekly for four weeks. at the end of 12 weeks, 77 percent of patients had complete clearance, 21 percent had partial clearance, and two percent were nonresponders. 138 When compared with diclofenac 3% in hyaluronic acid and vehicle, 5-fu 0.5% had greater histological and clinical clearance rates with durable benefts in the lesion-directed treatment of aK than the diclofenac with hyaluronic acid or vehicle. 139 in a placebo-controlled, double-blind, parallel- group, multicenter trial, aK patients were randomized to topical 5-fu 0.5% gel applied once daily, vehicle treatment, or diclofenac in hyaluronic acid twice daily. 140 Patients were treated for a maximum of 12 weeks, and lesion recurrence was evaluated at 6 and 12 months after the end of treatment. at 12 months, there was no recurrence of aK lesions in the 5-fu 0.5% gel group for 85.8 percent of patients compared to 79.8 percent of vehicle patients with no recurrence (p=0.04419) and 81.0 percent of patients in the diclofenac hyaluronic acid group (p=0.0246). adverse events occurred most frequently in the 5-fu group (ingammation, burning) but generally did not cause patients to discontinue treatment. 140 in a Phase 3 randomized, double-blind, vehicle- controlled multicenter study (n=166), patients with feld aK were randomized to receive either 5-fu 0.5% gel combined with salicylic acid 10% or vehicle applied topically once a day for 12 weeks (contiguous areas of the skin for 25cm 2 ). 141 the frst and last topical applications were performed by the study clinicians but otherwise patients applied the medication themselves. after eight weeks of treatments, the intention-to-treat and per-protocol populations of this study had signifcantly better results with 5-fu 0.5% gel and salicylic acid than the vehicle, 49.5 vs. 18.2 percent for intention-to-treat patients (odds ratio 3.9, 95% ci: 1.7–8.7, p=0.0006). Patients in the active- treatment group had more application and administration site reactions compared to figure 4. Proportional changes from baseline in the total number of aK lesions during and after treatment for 5-guorouracil 0.5% combined with salicylic acid 10% (n=108) vs. vehicle patients (n=55). 1 34 reproduced with permission from eggert stockgeth, MD. copyright © 2012

Articles in this issue

Archives of this issue

view archives of Journal of Clinical and Aesthetic Dermatology - Updates on Psoriasis & Cutaneou Oncology