Simon J-C, Dominicus R, Karl L, Rodríguez R, Willers C, Dirschka T
Department of Dermatology, Venereology and Allergology, University of Leipzig Medical Center, Leipzig, Germany.
J Eur Acad Dermatol Venereol. 2015 May;29(5):881-9. doi: 10.1111/jdv.12702. Epub 2014 Sep 25.
Actinic keratoses (AKs) are clinically significant and require therapy. Efficacy of low-dose (0.5%) 5-fluorouracil with 10% salicylic acid (5-FU/SA) has been shown in randomized comparative trials of hyperkeratotic lesions of various grades.
To evaluate the efficacy, tolerability and safety of low-dose 5-FU/SA topical solution vs. cryosurgery in patients with moderate/severe (grade II/III) hyperkeratotic AKs (NCT01358851).
In an exploratory, open, randomized study, patients with histologically confirmed moderate/severe hyperkeratotic AKs on the face/forehead or bald scalp received 6 weeks of once-daily topical 0.5% 5-FU/SA, or up to two cryosurgery treatments (3 weeks apart). Histological outcomes were determined from punch biopsies. Clinical, cosmetic and tolerability outcomes were also assessed.
Sixty-six patients received treatment (33 per arm). The baseline total number of lesions was 266 (8.1/patient) in the 0.5% 5-FU/SA and 263 (8.0/patient) in the cryosurgery group. Most (74.5%) lesions were grade II (grade III, 25.5%). Mean change in lesion count from baseline to Day 98 was -5.2 and -5.7 lesions per patient for 0.5% 5-FU/SA and cryotherapy groups respectively. Histological AK clearance rates on Day 98 were 62.1% and 41.9% respectively. At 6-month posttreatment follow-up, recurrence of cleared lesions (no clinically visible lesions in treatment area) occurred in 39.4% of 0.5% 5-FU/SA and 84.8% of cryosurgery patients. Drug-related adverse events (AEs), including local skin reactions considered 'severe' by the investigator, were reported in 24.2% of 0.5% 5-FU/SA and 6.1% of cryosurgery patients. All drug-related AEs were skin reactions.
Although the study was not powered to explore statistical differences in clinical efficacy between treatments, a short (6-week) schedule of topical treatment with 0.5% 5-FU/SA achieved greater histological clearance and lower recurrence of grade II/III hyperkeratotic AKs than cryosurgery. AE incidence across both treatment groups was relatively low and AEs were generally mild or moderate. Clinical trials.gov identifier: NCT01358851.
光化性角化病（AKs）具有临床意义，需要进行治疗。在不同等级的角化过度性病变的随机对照试验中，已证实低剂量（0.5%）5-氟尿嘧啶与10%水杨酸（5-FU/SA）联合使用具有疗效。
评估低剂量5-FU/SA外用溶液与冷冻手术治疗中度/重度（II/III级）角化过度性AKs患者（NCT01358851）的疗效、耐受性和安全性。
在一项探索性、开放性、随机研究中，面部/前额或秃发头皮组织学确诊为中度/重度角化过度性AKs的患者接受为期6周的每日一次外用0.5% 5-FU/SA治疗，或接受最多两次冷冻手术治疗（间隔3周）。通过打孔活检确定组织学结果。还评估了临床、美容和耐受性结果。
66例患者接受了治疗（每组33例）。0.5% 5-FU/SA组病变总数基线为266个（8.1个/患者），冷冻手术组为263个（8.0个/患者）。大多数（74.5%）病变为II级（III级占25.5%）。从基线到第98天，0.5% 5-FU/SA组和冷冻治疗组患者的病变计数平均变化分别为每位患者-5.2个和-5.7个。第98天时组织学AK清除率分别为62.1%和41.9%。治疗后6个月随访时，0.5% 5-FU/SA组39.4%的患者和冷冻手术组84.8%的患者出现清除病变复发（治疗区域无临床可见病变）。0.5% 5-FU/SA组24.2%的患者和冷冻手术组6.1%的患者报告了与药物相关的不良事件（AE），包括研究者认为“严重”的局部皮肤反应。所有与药物相关的AE均为皮肤反应。
尽管该研究没有足够的能力来探究两种治疗方法在临床疗效上统计学差异，但0.5% 5-FU/SA的短期（6周）外用治疗方案比冷冻手术在组织学清除方面效果更好，II/III级角化过度性AKs的复发率更低。两个治疗组的AE发生率相对较低，且AE一般为轻度或中度。ClinicalTrials.gov标识符：NCT01358851。
