NCT07362914

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

The Role of Corticosteroids in Hand & Foot & Skin Reactions Reduction to Doxorubicin Liposomes

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 182 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Investigating the Association Between Corticosteroid Use and Improvement in Doxorubicin Liposome-Induced Cutaneous Toxicity: Exploring the Feasibility and Mechanisms of Corticosteroids in Mitigating Liposomal Doxorubicin-Related Dermatologic Adverse Effects.

Detailed description

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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Dexamethasone (12mg d1)	dexamethasone 12mg d1, PO/IV;
DRUG	Dexamethasone (2mg QD, d1-5,)	dexamethasone 12mg QD, d1-5, PO/IV.
DRUG	Doxorubicin hydrochloride liposome injection	Liposomal doxorubicin at a dose of 35 mg/m², given via intravenous (IV) infusion every 2 weeks (q2w) or every 3 weeks (q3w).
DRUG	Cyclophosphamide	Cyclophosphamide 600 mg/m² administered by intravenous infusion every 2 weeks (q2w) or every 3 weeks (q3w).

Timeline

• Start date: 2025-03-07
• Primary completion: 2026-07-30
• Completion: 2027-01-30
• First posted: 2026-01-23
• Last updated: 2026-01-23

Locations

1 site across 1 country: China