Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial
Frederik Gulmark Hansen, Mads Gustaf Jørgensen, Jens Ahm Sørensen
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.