Hansen Frederik Gulmark, Jørgensen Mads Gustaf, Thomsen Jørn Bo, Sørensen Jens Ahm
Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark.
Clinical Institute, University of Southern Denmark, Odense, Denmark.
Trials. 2025 Apr 8;26(1):127. doi: 10.1186/s13063-025-08829-3.
Breast cancer-related lymphedema is a chronic condition affecting 15-30% of breast cancer patients, resulting from treatment-related inflammation and fibrosis primarily mediated by CD4 + T-cells. Tacrolimus, an immunomodulator, has shown efficacy in reducing lymphedema in both animal models and an initial clinical trial. This study aims to validate these findings in a larger cohort, hypothesizing that tacrolimus will reduce lymphedema volume, fibrosis, and fluid retention while improving quality of life.
This multicenter, double-blinded, randomized placebo-controlled trial will enroll 80 women with breast cancer-related lymphedema stages I and II. Participants will be randomized 1:1 to receive either 0.1% tacrolimus ointment or a placebo ointment for 12 months. Primary outcome will be the change in lymphedema volume measured at baseline, 6 months, and 12 months. Secondary outcomes include quality of life assessed via SF- 36, DASH, and LYMPH-Q Upper Extremity questionnaires; lymphedema index via bioimpedance spectroscopy; lymphatic function and flow via indocyanine green lymphangiography; and skin fibrosis measurement. Assessments will take place at baseline, 3, 6, 9, and 12 months.
This trial will provide robust data on the efficacy of topical tacrolimus in reducing BCRL volume and improving patient quality of life. Positive results could establish tacrolimus as a standard treatment for BCRL, potentially enhancing clinical outcomes for affected patients. The findings will also contribute to understanding the role of immunomodulation in lymphedema management.
This trial is registered with the EU Clinical Trials Information System (CTIS) under EU CT Number: 2023-503644 - 13-00 (approved 16.05.2024) and ClinicalTrials.gov under identifier NCT06306274 (registered 12.03.2024).
乳腺癌相关淋巴水肿是一种慢性病，影响15%至30%的乳腺癌患者，由治疗相关的炎症和纤维化引起，主要由CD4 + T细胞介导。他克莫司作为一种免疫调节剂，在动物模型和一项初步临床试验中均显示出减轻淋巴水肿的功效。本研究旨在通过更大的队列验证这些发现，假设他克莫司将减少淋巴水肿体积、纤维化和液体潴留，同时改善生活质量。
这项多中心、双盲、随机安慰剂对照试验将招募80名患有I期和II期乳腺癌相关淋巴水肿的女性。参与者将按1:1随机分组，接受0.1%他克莫司软膏或安慰剂软膏治疗12个月。主要结局将是在基线、6个月和12个月时测量的淋巴水肿体积变化。次要结局包括通过SF-36、DASH和LYMPH-Q上肢问卷评估的生活质量；通过生物电阻抗光谱法测量的淋巴水肿指数；通过吲哚菁绿淋巴管造影术测量的淋巴功能和流量；以及皮肤纤维化测量。评估将在基线、3个月、6个月、9个月和12个月时进行。
本试验将提供关于外用他克莫司减轻乳腺癌相关淋巴水肿体积和改善患者生活质量疗效的有力数据。阳性结果可能会确立他克莫司作为乳腺癌相关淋巴水肿的标准治疗方法，有可能改善受影响患者的临床结局。这些发现也将有助于理解免疫调节在淋巴水肿管理中的作用。
本试验已在欧盟临床试验信息系统（CTIS）注册，欧盟临床试验编号为：2023-503644 - 13-00（2024年5月16日批准），并在ClinicalTrials.gov注册，标识符为NCT06306274（2024年3月12日注册）。
