The protective role of Deferoxamine in the prevention of hepatic fibrosis in children treated with Doxorubicin: a randomized controlled clinical trial

Abstract Background: Hepatic fibrosis is an ominous sign which may follow treatment with Doxorubicin (DOX) chemotherapy. The aim of this study was investigating the protective effect of Deferoxamine (DFO) against hepatic fibrosis in treatment-naïve 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: Fifty-six patients were analyzed. Alanine aminotransferase was mildly increased in the treatment groups compared to pre-treatment. Treatment with DFO 10 times DOX dose was associated with significant decline in post-treatment APRI (adjusted odds ratio 0.17; 95% confidence interval 0.03- 0.84). METAVIR fibro scores were in the F0-F1 zone in all participants, and the results were comparable in the study groups. No adverse drug effect was reported in the treatment groups. Conclusion: DOX may not lead to severe liver fibrosis if the maximum allowed cumulative dose 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 up are warranted to further assess this issue.