Abstract：
BACKGROUND: No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget\'s disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD.
METHODS: In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period.
RESULTS: All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated.
CONCLUSIONS: The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).
METHODS: In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period.
RESULTS: All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated.
CONCLUSIONS: The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).
摘要：
背景：关于转移性乳腺外Paget病（EMPD）的最佳化疗方案尚未达成共识，罕见的皮肤腺癌,因为缺乏来自前瞻性试验的确凿证据。然而,据报道，EMPD的免疫组织化学特征与乳腺癌相似，特别是在人类表皮生长因子受体2（HER2）表达方面，提示HER2是晚期HER2阳性EMPD的有希望的治疗靶点。
方法：在这项II期单臂试验中，13名日本患者每3周接受静脉注射曲妥珠单抗（负荷剂量为8mg/kg，维持剂量为6mg/kg）和多西他赛（75mg/m2），为期2年。多西他赛剂量根据其毒性减少或中断。主要试验终点是3个治疗周期后的客观反应率（ORR）和整个研究期间的安全性。
结果：所有13例患者均完成了3个周期的联合治疗。中位随访时间为27.9个月。ORR为76.9%(n=10/13;90%CI,50.5-93.4)。经常观察到的不良事件是中性粒细胞减少症（100％），低蛋白血症（84.6%），皮肤粘膜感染（84.6%），所有这些都是很好的耐受性。
结论：多西他赛和曲妥珠单抗的联合使用显示出良好的临床效果和可接受的耐受性，这使其成为HER2阳性转移性EMPD的良好治疗选择（ClinicalTrials.gov标识符：UMIN000021311，jRCTs031180073）。
方法：在这项II期单臂试验中，13名日本患者每3周接受静脉注射曲妥珠单抗（负荷剂量为8mg/kg，维持剂量为6mg/kg）和多西他赛（75mg/m2），为期2年。多西他赛剂量根据其毒性减少或中断。主要试验终点是3个治疗周期后的客观反应率（ORR）和整个研究期间的安全性。
结果：所有13例患者均完成了3个周期的联合治疗。中位随访时间为27.9个月。ORR为76.9%(n=10/13;90%CI,50.5-93.4)。经常观察到的不良事件是中性粒细胞减少症（100％），低蛋白血症（84.6%），皮肤粘膜感染（84.6%），所有这些都是很好的耐受性。
结论：多西他赛和曲妥珠单抗的联合使用显示出良好的临床效果和可接受的耐受性，这使其成为HER2阳性转移性EMPD的良好治疗选择（ClinicalTrials.gov标识符：UMIN000021311，jRCTs031180073）。
