双甘醇抗坏血酸预防手足皮肤反应的安全性和有效性：一项单臂、开放标签的 I/II 期研究（DGA 研究）。
Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study).
机构信息
Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
出版信息
Oncologist. 2022 May 6;27(5):e384-e392. doi: 10.1093/oncolo/oyab067.
BACKGROUND
Hand-foot skin reaction (HFSR) induced by multiple tyrosine kinase inhibitors (TKIs) is a serious side effect that can cause treatment interruption or decreased dosing. This study was conducted to evaluate the safety and efficacy of bis-glyceryl ascorbate (Amitose bis(di)-glyceryl ascorbate [DGA])-containing cream (DGA cream) for the prevention of sunitinib-induced HFSR.
METHODS
A single-arm, open-label phase I/II study was conducted, targeting patients with metastatic renal cell carcinoma (mRCC) who were receiving sunitinib therapy with a schedule of 2 weeks on/1 week off. The participants applied DGA cream to both palmar and plantar surfaces in combination with a moisturizing agent as standard-of-care prophylaxis during two sunitinib treatment cycles (6 weeks). The primary endpoint in phase I was safety defined as dermatological abnormalities and it was determined in the first five participants. The primary endpoint in phase II was efficacy defined as development of grade 1 or higher HFSR defined by Common Terminology Criteria for Adverse Events within 6 weeks and it was determined on a full analysis set (FAS) defined as the population including all participants who used DGA cream once in the study duration. Efficacy in the per protocol set (PPS) defined as the population excluding seven patients whose study treatment was interrupted was evaluated as a secondary endpoint.
RESULTS
Twenty-four patients were enrolled as a FAS. No dermatological abnormalities occurred in the first 5 patients enrolled in the phase I study. Three patients developed HFSR (grade 1: n = 2, grade 2: n = 1) in the observation period. The HFSR incidence rate was 12.5% (3/24; 95% confidence interval [CI]: 2.7%-32.4%) in the FAS, which was significantly lower than the incidence rate predefined as a threshold of 33.3% by a previous report from our hospital (P = .030). The incidence rate in the 17 patients of the PPS was 17.6% (3/17; 95%CI: 3.8%-43.4%).
CONCLUSION
DGA cream may be safe and effective in the prophylaxis of HFSR in mRCC patients who receive sunitinib therapy (Trial ID: jRCTs051180051).
背景
多种酪氨酸激酶抑制剂（TKI）引起的手足皮肤反应（HFSR）是一种严重的副作用，可导致治疗中断或减少剂量。本研究旨在评估含有双甘油抗坏血酸（Amitose bis(di)-glyceryl ascorbate [DGA]）的乳膏（DGA 乳膏）预防舒尼替尼引起的 HFSR 的安全性和疗效。
方法
这是一项单臂、开放标签的 I/II 期研究，纳入了接受舒尼替尼治疗的转移性肾细胞癌（mRCC）患者，舒尼替尼的治疗方案为 2 周用药/1 周停药。在两个舒尼替尼治疗周期（6 周）中，参与者将 DGA 乳膏涂抹于手掌和足底表面，并联合保湿剂作为标准预防措施。I 期的主要终点是安全性，定义为皮肤异常，在最初的 5 名参与者中确定。II 期的主要终点是疗效，定义为在 6 周内发生根据不良事件通用术语标准定义的 1 级或更高 HFSR，并在全分析集（FAS）中确定，FAS 人群包括所有在研究期间使用过 DGA 乳膏一次的参与者。排除 7 名研究治疗中断的患者的方案符合集（PPS）中的疗效为次要终点。
结果
24 名患者被纳入 FAS。I 期研究中最初纳入的 5 名患者未出现皮肤异常。在观察期内，有 3 名患者发生 HFSR（1 级：n=2，2 级：n=1）。FAS 中 HFSR 的发生率为 12.5%（3/24；95%置信区间[CI]：2.7%-32.4%），明显低于我院既往报告预设的 33.3%的阈值（P=0.030）。PPS 中 17 名患者的发生率为 17.6%（3/17；95%CI：3.8%-43.4%）。
结论
DGA 乳膏可能对接受舒尼替尼治疗的 mRCC 患者预防 HFSR 安全且有效（试验 ID：jRCTs051180051）。
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