Cardioprotective effects of deferoxamine in acute and subacute cardiotoxicities of doxorubicin: a randomized clinical trial

Kosar Rahimi; Hamid Amoozgar; Soheila Zareifar; Mahdi Shahriari; Omid Reza Zekavat; Mehran Karimi; Gholamreza Fathpour; Fazl Saleh; Nader Shakibazad; Shayan Bordbar; Mohammadreza Bordbar

doi:10.1186/s43044-023-00347-4

Cardioprotective effects of deferoxamine in acute and subacute cardiotoxicities of doxorubicin: a randomized clinical trial

Egypt Heart J. 2023 Mar 24;75(1):21. doi: 10.1186/s43044-023-00347-4.

Authors

Affiliations

¹ Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran.
² Department of Pediatrics, and Divisions of Pediatric Cardiology, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ Department of Pediatrics, and Divisions of Pediatric Hematology and Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.
⁵ Bushehr University of Medical Sciences, Bushehr, Iran.
⁶ Students Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
⁷ Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. mbordbar53@gmail.com.

Abstract

Background: Cardiotoxicity is a major concern following doxorubicin (DOX) use in the treatment of malignancies. We aimed to investigate whether deferoxamine (DFO) can prevent acute cardiotoxicity in children with cancer who were treated with DOX as part of their chemotherapy.

Results: Sixty-two newly-diagnosed pediatric cancer patients aged 2-18 years with DOX as part of their treatment regimens were assigned to three groups: group 1 (no intervention, n = 21), group II (Deferoxamine (DFO) 10 times DOX dose, n = 20), and group III (DFO 50 mg/kg, n = 21). Patients in the intervention groups were pretreated with DFO 8-h intravenous infusion in each chemotherapy course during and after completion of DOX infusion. Conventional and tissue Doppler echocardiography, serum concentrations of human brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were checked after the last course of chemotherapy. Sixty patients were analyzed. The level of cTnI was < 0.01 in all patients. Serum BNP was significantly lower in group 3 compared to control subjects (P = 0.036). No significant differences were observed in the parameters of Doppler echocardiography. Significant lower values of tissue Doppler late diastolic velocity at the lateral annulus of the tricuspid valve were noticed in group 3 in comparison with controls. By using Pearson analysis, tissue Doppler systolic velocity of the septum showed a marginally significant negative correlation with DOX dose (P = 0.05, r = - 0.308). No adverse effect was reported in the intervention groups.

Conclusions: High-dose DFO (50 mg/kg) may serve as a promising cardioprotective agent at least at the molecular level in cancer patients treated with DOX. Further multicenter trials with longer follow-ups are needed to investigate its protective role in delayed DOX-induced cardiac damage. Trial registration IRCT, IRCT2016080615666N5. Registered 6 September 2016, http://www.irct.ir/IRCT2016080615666N5 .

Keywords: Cancer; Cardiotoxicity; Deferoxamine; Doxorubicin; Pediatric.

Grants and funding

93-01-01-8499/Vice-Chancellor for Research, Shiraz University of Medical Sciences