Effectiveness and safety of 5% nicotinamide cream following cryosurgery in skin field cancerization: a randomized, double-blind, placebo-controlled clinical trial

Abstract

Abstract Individuals with multiple actinic keratoses (AKs) in the same area have an active skin field cancerization (SFC). The treatment of AKs and SFC reduces the recurrence of AKs and the appearance of squamous cell carcinomas (SCCs). Recently, oral nicotinamide (NIC) was proposed as effective in the chemoprevention of SCC and AKs, but there have been no clinical trials with topical NIC as a treatment for AKs and SFC. Thus, we conducted a prospective, randomized, double-blind, self-controlled trial to evaluate the efficacy and safety of 5% NIC cream in treating SFC after cryotherapy with liquid nitrogen (NL) for AKs. Subjects with between three and 10 AKs on the forearms received cryotherapy with NL on the AKs, and the forearms were randomized to receive: 5% NIC cream b.i.d. for 56 days or placebo cream (PLAC) at the same dosage, started 14 days after NL. The primary outcome was the percentage reduction in the AK count on D70. Secondary endpoints were the complete clearance and reduction of SFC activity at D70. The sample size was defined to detect a difference higher than 15% between the groups (power of 0.9, alpha of 0.05, and dropout estimate of 10%), which resulted in 40 forearms per group. After 70 days, there was a 61% (95% CI 50─72%) reduction in the AK count in NIC versus 56% (95% CI 44─68%) in PLAC (p = 0.698). Complete clearance was achieved in 21% (95% CI 7─37%) of NIC versus 17% (95% CI 4─31%) of PLAC (p = 0.440). An interim analysis was performed after the last evaluation of the 26th subject, and the difference between the groups did not reach 15%; thus, the study was discontinued due to futility. No adverse effects were reported. Our results suggest that in the treatment of inflammatory dermatoses, the anti-inflammatory capacity of NIC is not sufficient to reduce SFC activity. The present study has limitations: it is monocentric with homogeneous subjects and a short duration between intervention and follow-up. Topical treatment with 5% NIC was safe in immunocompetent adults with AK and SFC; however, it was not superior to placebo in reducing AKs or SFC activity.