Cardioprotection by ICRF187 against high dose anthracycline toxicity in children with malignant disease.
OBJECTIVE
A pilot study to assess the efficacy of ICRF187 as a protective agent against the cardiotoxic effects of anthracycline drugs used to treat childhood malignancies.


METHODS
A study of cardiac function in children treated receiving ICRF187 ((s)-(+)-1,2 bis (3,5-dioxopiperazenyl) propane) in addition to anthracycline therapy compared with contemporary controls selected retrospectively on the basis of anthracycline dose matching.


METHODS
Five children in whom recurrence of malignant disease was re-treated with chemotherapy containing anthracycline drugs and additional ICRF187 (supplied on a compassionate-use basis) (cumulative anthracycline doses 550-1650 mg/m2). Five more children with recurrence of malignant disease were re-treated to similar cumulative anthracycline doses (600-1150 mg/m2) without ICRF187.


METHODS
Cardiac function was assessed clinically and echocardiographically throughout treatment. Clinical and echocardiographic state were compared before treatment and after completion of therapy within and between groups treated with and without ICRF187.


RESULTS
Two patients treated without ICRF187 developed symptomatic congestive cardiac failure from which one died. Another developed considerable but as yet asymptomatic left ventricular dysfunction. No patient receiving additional ICRF187 developed cardiac failure or left ventricular dysfunction. There were no significant differences in cumulative anthracycline dose, dose increase, type of anthracycline used, survival rate, or length of survival between groups. Left ventricular shortening fraction fell by a mean of 1.0% in patients receiving ICRF187 and by a mean of 11% in the patients treated without it (p = 0.04).


CONCLUSIONS
ICRF187 seems to have provided highly effective cardioprotection to this small group of children with end-stage malignancy. Severe cardiotoxicity was seen in a similar group treated with comparable anthracycline doses but without ICRF187.
Department of Paediatric Cardiology, Bristol Royal Hospital for Sick Children.
F A
FA
Bu'Lock
H M
HM
Gabriel
A
A
Oakhill
M G
MG
Mott
R P
RP
Martin
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D011929:Razoxane / Q000494:pharmacology / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D011929:Razoxane