CMB Collegium Medicum Berlin GmbH, Berlin, Germany.
Dermatological Center Bonn Friedensplatz, Bonn, Germany.
J Eur Acad Dermatol Venereol. 2018 Mar;32(3):390-396. doi: 10.1111/jdv.14611. Epub 2017 Oct 19.
Actinic keratosis (AK) is a common skin disorder that can progress to invasive squamous-cell carcinoma. AK can present as clinical (visible) or subclinical (invisible) lesions within areas of chronic sun damage. The importance of treating subclinical AK is gaining support. We present a subanalysis of a previously published Phase III, double-blind, vehicle-controlled study (NCT02289768), to assess 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% treatment of subclinical AK lesions, based on reflectance confocal microscopy (RCM).
To determine the efficacy of 5-FU 0.5%/salicylic acid 10% as field-directed treatment for subclinical AK lesions using RCM.
For inclusion in this subanalysis, patients had to have at least three subclinical AK lesions within a 25 cm area of skin. Subclinical AK lesions were diagnosed according to the presence of three key RCM criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Subclinical AK lesions were evaluated by RCM at baseline, after 4, 6 and 12 weeks of 5-FU 0.5%/salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment.
Twenty-seven patients were included: 17 [mean age = 72.2 years, standard deviation (SD) = 6.3] received 5-FU 0.5%/salicylic acid 10% treatment and 10 (mean age = 76.4 years, SD = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of subclinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [CI] 0.06-0.57) for the 5-FU 0.5%/salicylic acid 10% group and 1.6 (95% CI 0.52-2.68) in the vehicle group (reductions of 90% [95% CI 72.1-107.1] vs. 47% [95% CI 24.8-69.5], respectively; P = 0.005). The proportion of patients receiving 5-FU 0.5%/salicylic acid 10% showing complete clearance of three preselected subclinical AK lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively; P = 0.183).
To the best of our knowledge, this is the first randomized, vehicle-controlled study investigating 5-FU 0.5%/salicylic acid 10% treatment for subclinical AK lesions. The present data suggest some treatment efficacy for subclinical AK lesions detected using RCM. However, this subanalysis was not sufficiently powered and should be reproduced in a larger, subsequent cohort.
光化性角化病（AK）是一种常见的皮肤疾病，可进展为侵袭性鳞状细胞癌。AK 可表现为慢性阳光损伤区域内的临床（可见）或亚临床（不可见）病变。治疗亚临床 AK 的重要性越来越受到重视。我们报告了先前发表的一项 III 期、双盲、安慰剂对照研究（NCT02289768）的亚分析结果，该研究使用反射共聚焦显微镜（RCM）评估了 5-氟尿嘧啶（5-FU）0.5%/水杨酸 10%治疗亚临床 AK 病变的疗效。
根据 RCM 确定 5-FU 0.5%/水杨酸 10%作为亚临床 AK 病变的定向治疗的疗效。
为纳入本亚分析，患者必须在 25 cm 皮肤区域内至少有三个亚临床 AK 病变。亚临床 AK 病变根据三个关键 RCM 标准的存在进行诊断：结构紊乱；基底层、棘层和颗粒层的角质形成细胞异型性和多形性。基线时使用 RCM 评估亚临床 AK 病变，在接受 5-FU 0.5%/水杨酸 10%或安慰剂治疗 4、6 和 12 周以及治疗结束后 8 周时进行评估。
纳入了 27 名患者：17 名[平均年龄=72.2 岁，标准差（SD）=6.3]接受 5-FU 0.5%/水杨酸 10%治疗，10 名（平均年龄=76.4 岁，SD=3.9）接受安慰剂。治疗结束后 8 周，5-FU 0.5%/水杨酸 10%组的平均亚临床病变数量从基线时的 3.0 下降至 0.3（95%置信区间[CI]0.06-0.57），而安慰剂组为 1.6（95% CI 0.52-2.68）（分别减少 90%[95%CI72.1-107.1]和 47%[95%CI24.8-69.5]；P=0.005）。接受 5-FU 0.5%/水杨酸 10%治疗的患者中，完全清除三个预先选定的亚临床 AK 病变的比例数值上大于安慰剂组（分别为 69%和 40%；P=0.183）。
据我们所知，这是第一项使用 RCM 调查 5-FU 0.5%/水杨酸 10%治疗亚临床 AK 病变的随机、安慰剂对照研究。目前的数据表明，RCM 检测到的亚临床 AK 病变存在一定的治疗效果。然而，本亚分析的效力不足，应在更大的后续队列中进行复制。
