Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence, Florence, Italy.
J Eur Acad Dermatol Venereol. 2016 Jul;30(7):1129-32. doi: 10.1111/jdv.13616. Epub 2016 Apr 13.
'Hydroxyurea-induced Squamous Dysplasia' (HISD) is a cutaneous side-effect related to chronic oral treatment with Hydroxyurea. Ingenol mebutate gel is a topical drug approved for the treatment of multiple, non-hypertrophic actinic keratoses (AK) localized within a limited cancerization field. Since HISD may be considered as a drug-induced variant of classic AK, ingenol mebutate is likely to have therapeutic effects.
The aim of this study was to evaluate efficacy and safety of ingenol mebutate 150 mcg/g and 500 mcg/g, as a treatment of HISD lesions on face/scalp and trunk/extremities respectively.
Seven areas with a mean of lesions of 5.9 ± 1.7 in five patients with HISD were treated. Patients with lesions on face/scalp self-treated a 25 cm(2) skin affected area with ingenol mebutate gel 150 mcg/g, one tube daily for 3 days. Patients with lesions localized on trunk/extremities treated the same size affected area with ingenol mebutate gel 500 mcg/g, one tube daily for 2 days. Clinical assessment and count of HISD lesions has been performed by an experienced dermatologist at day 0, at day 57, and at time of last feasible follow-up visit (median 337 days). Safety assessment included the report of all SAEs.
At 57-day follow-up, we observed an overall response rate (ORR) - the sum of Complete Responses (CR) + Partial Responses (PR) - of 87.5%, with a 57.1% CR, and a 78.0% total lesions' reduction compared to time 0 (P < 0.01). On a median follow-up of 337 days, we observed a long-term ORR of 71.4%, a 57.1% CR ratio and a 65.9% total lesions' reduction compared to time 0 (P = 0.01). No severe (grade 3-4) adverse events have been reported.
Although obtained in a small case series, these encouraging data lead us to propose ingenol mebutate gel as a possible treatment for HISD.
“羟基脲诱导的鳞状发育不良”（HISD）是一种与羟基脲慢性口服治疗相关的皮肤副作用。Ingenol 美泊丁酸凝胶是一种局部用药物，已被批准用于治疗多个局限性癌化区域内的非肥大性光化性角化病（AK）。由于 HISD 可被视为经典 AK 的药物诱导变异型，因此 ingenol 美泊丁酸凝胶可能具有治疗效果。
本研究旨在评估 ingenol 美泊丁酸凝胶 150 mcg/g 和 500 mcg/g 分别用于面部/头皮和躯干/四肢 HISD 病变的疗效和安全性。
对 5 例 HISD 患者的 7 个区域（每个区域平均病变 5.9 ± 1.7 个）进行治疗。面部/头皮病变患者使用 ingenol 美泊丁酸凝胶 150 mcg/g 自行治疗 25 cm² 的皮肤受累区域，每天一管，连续 3 天。躯干/四肢病变患者使用 ingenol 美泊丁酸凝胶 500 mcg/g 治疗相同大小的受累区域，每天一管，连续 2 天。在第 0 天、第 57 天和最后一次可行的随访（中位随访时间为 337 天）时，由经验丰富的皮肤科医生进行临床评估和 HISD 病变计数。安全性评估包括所有严重不良事件（SAE）的报告。
在第 57 天随访时，我们观察到总缓解率（ORR）-完全缓解（CR）+部分缓解（PR）的总和为 87.5%，其中 CR 为 57.1%，与基线相比，总病变减少了 78.0%（P < 0.01）。在中位随访 337 天时，我们观察到长期 ORR 为 71.4%，CR 为 57.1%，总病变减少了 65.9%（与基线相比，P = 0.01）。未报告严重（3-4 级）不良事件。
尽管这是在一个小病例系列中获得的数据，但这些令人鼓舞的数据使我们提出 ingenol 美泊丁酸凝胶可能是治疗 HISD 的一种方法。
