Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial.

IF 2.2 4区医学 Q3 ONCOLOGY

Journal of Breast Cancer Pub Date : 2023-02-01 DOI:10.4048/jbc.2023.26.e2

Frederik C Gulmark Hansen, Mads Gustaf Jørgensen, Jens Ahm Sørensen

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引用次数: 4

Abstract

Purpose: Breast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy. Cluster of differentiation 4-positive (CD4⁺) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis. Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4⁺ cells. Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials. This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology.

Methods: We conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021. Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months. The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design.

Results: The mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05). According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening. Lymph flow or function showed no change according to the Arm Dermal Backflow scale.

Conclusion: In this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL. Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL. Assessments of lymph flow and function were positive, although inconclusive. Larger randomized controlled trials are required to verify these findings.

Trial registration: ClinicalTrials.gov Identifier: NCT04541290.

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局部他克莫司治疗乳腺癌相关淋巴水肿:一项前瞻性、开放标签、单臂、II期试点试验

目的:乳腺癌相关淋巴水肿(Breast cancer-related lymphodema, BCRL)是乳腺癌治疗的一种慢性进行性副作用，在接受腋窝淋巴结清扫和淋巴结放疗的患者中有三分之一发生。分化4阳性(CD4+)细胞簇通过促进炎症和抑制淋巴管生成在BCRL中起关键作用。他克莫司是一种针对CD4+细胞的抗炎和免疫抑制大环内酯类药物。局部他克莫司治疗淋巴水肿在临床前试验中显示出有希望的结果。根据国际淋巴学会的说法，该临床试验旨在评估他克莫司治疗I期或II期BCRL的可行性、安全性和效果。方法:我们于2020年9月至2021年4月进行了这项开放标签、单臂、II期试点试验。18名患有I期或II期BCRL的女性接受局部他克莫司治疗6个月，并在3个月和6个月时随访。主要终点是臂体积，次要终点是淋巴水肿指数(L-Dex)、健康相关生活质量(HRQoL)、淋巴流量和功能，以及试验设计的安全性和可行性。结果:大鼠淋巴水肿臂平均体积、L-Dex减少130.44±210.13 mL (p < 0.05);相对降低3.6%)和3.54±4.98 (p < 0.05)，健康相关生活质量评分显著提高(p < 0.05)。根据MD Anderson评分，在淋巴流动和功能方面，3例(16.7%)患者表现出改善，没有患者表现出恶化。根据手臂皮肤回流量表，淋巴流量或功能未见变化。结论:在本试验中，他克莫司对I期或II期BCRL患者的治疗是安全可行的。他克莫司在改善臂体积、L-Dex和HRQoL方面减轻了BCRL。淋巴流动和功能的评估是阳性的，尽管不确定。需要更大规模的随机对照试验来验证这些发现。试验注册:ClinicalTrials.gov标识符:NCT04541290。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Breast Cancer 医学-肿瘤学

CiteScore

3.80

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Breast Cancer (abbreviated as ''J Breast Cancer'') is the official journal of the Korean Breast Cancer Society, which is issued quarterly in the last day of March, June, September, and December each year since 1998. All the contents of the Journal is available online at the official journal website (http://ejbc.kr) under open access policy. The journal aims to provide a forum for the academic communication between medical doctors, basic science researchers, and health care professionals to be interested in breast cancer. To get this aim, we publish original investigations, review articles, brief communications including case reports, editorial opinions on the topics of importance to breast cancer, and welcome new research findings and epidemiological studies, especially when they contain a regional data to grab the international reader''s interest. Although the journal is mainly dealing with the issues of breast cancer, rare cases among benign breast diseases or evidence-based scientifically written articles providing useful information for clinical practice can be published as well.