The protective role of deferoxamine in the prevention of doxorubicin-induced hepatic fibrosis in children: A randomized controlled clinical trial

Background: This study aimed to investigate the protective effects of Deferoxamine (DFO) against hepatic fibrosis in treatment of pediatric cancer patients. Methods: In this prospective randomized controlled trial, 61 treatment-naïve children (2-18 years) with different types of cancer who referred to a tertiary teaching hospital in South of Iran were enrolled. They were randomly assigned to 3 groups; group 1 (control, n=21), group 2 (DFO 10 times DOX dose, n=20), group 3 (DFO 50mg/kg, n=20). DFO was administered as an 8-hour continuous intravenous infusion during and after DOX infusion in each chemotherapy cycle. Non-invasive serum markers of liver fibrosis including APRI, FIB-4 score and Fibro Test were measured in each individual. Besides, hepatic Fibro Scan was used after the last course of chemotherapy to estimate fibrosis degree. Results: Alanine aminotransferase was mildly increased in the treatment groups compared to the pre-treatment one. The treatment with DFO 10 times DOX dose was associated with a significant decline in post-treatment APRI (adjusted odds ratio 0.17; 95% confidence interval 0.03- 0.84. P.value=0.015). The METAVIR fibro scores were in the F0-F1 zone in all participants, and the results were comparable in study groups. No adverse drug effects were reported in the treatment groups. Conclusion: DOX may not lead to severe liver fibrosis if the maximum cumulative dose allowed is not exceeded. DFO at the dose of 10 times of DOX dose   may have a potential protective role against liver fibrosis. Larger multi-center studies with longer follow ups are needed to further assess this issue.