A Phase II clinical trial of idarubicin administered to children with relapsed brain tumors.
BACKGROUND
Idarubicin (IDR), an anthracycline that is a derivative of daunorubicin, was synthesized in an attempt to find new analogs of daunorubicin with an improved spectrum of activity and diminished acute or chronic toxicity. Because of the favorable pharmacokinetic profile of IDR (with the persistence of its active metabolite [idarubicinol], the penetration of idarubicinol into the cerebrospinal fluid, and the lipophilicity of IDR/idarubicinol compared with other anthracyclines), its more favorable therapeutic index regarding cardiotoxicity in animals, and its potential for oral administration, a Phase II trial of IDR in children with relapsed brain tumors was undertaken.


METHODS
Patients received IDR at a dose of 5 mg/m2/day x 3 days by intravenous bolus, followed by granulocyte-colony stimulating factor (G-CSF) at a dose of 5 microg/kg/day, starting on Day 7 of each cycle and continuing for at least 7 days, until the absolute neutrophil count was > or =10,000/mm3.


RESULTS
Three of 19 patients with high grade astrocytoma achieved a partial response, 1 of 20 patients with medulloblastoma had a complete response, and 0 of 13 patients with ependymoma and 0 of 13 patients with brainstem tumors had responses. In nine other brain tumor patients there were no responses. The most significant toxicity was myelosuppression.


CONCLUSIONS
IDR, given at a dose of 5 mg/m2/day x 3 days, is not sufficiently active against relapsed medulloblastoma, ependymoma, or brain stem tumors to warrant further study of this agent in a Phase III setting. The response rate for patients with relapsed high grade astrocytoma was 15% (95% confidence interval, 3.3-40%).
Arndt
C A
CA
Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
Krailo
M D
MD
Steinherz
L
L
Scheithauer
B
B
Liu-Mares
W
W
Reaman
G H
GH
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001933:Brain Stem / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004806:Ependymoma / Q000188:drug therapy / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000473:pathology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000188:drug therapy / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D016179:Granulocyte Colony-Stimulating Factor; D015255:Idarubicin