Corticosteroids for Doxorubicin Liposome-Induced Hand-Foot-Skin Reactions

Background Liposomal doxorubicin exhibits distinct toxicity profiles compared to free-form doxorubicin in clinical practice. Cutaneous toxicity represents the primary dose-limiting adverse effect of liposomal doxorubicin, with incidence and severity demonstrating a dose-dependent relationship . Current management strategies-including dose reduction or extended treatment intervals-yield limited efficacy, often leading to treatment discontinuation due to intolerable symptoms, thereby compromising clinical utility. Mechanistic Insights Our preliminary research identified neutrophils as key mediators in liposomal skin accumulation: Complement receptor 3 (CR3) recognizes iC3b deposited on liposomes via complement activation. Neutrophils phagocytose liposomes and extravasate into cutaneous tissues, driving drug accumulation. Intervention with complement inhibitors significantly reduced liposomal doxorubicin deposition in murine skin by: Blocking complement activation Decreasing iC3b opsonization Inhibiting neutrophil-mediated uptake. Clinical Evidence A retrospective study at our center demonstrated that corticosteroid pretreatment alleviated liposomal doxorubicin-induced hand-foot syndrome (HFS) in a dose-dependent manner : High-dose corticosteroids limited Grade 1 HFS to \<10% of patients16. Findings support complement inhibition as a viable strategy for mitigating cutaneous toxicity7. Study Objectives This prospective study aims to: Correlate corticosteroid use with HFS severity reduction in liposomal doxorubicin therapy.