TY - JOUR
T1 - A phase II clinical trial of idarubicin administered to children with relapsed brain tumors
AU - Arndt, Carola A.S.
AU - Krailo, Mark D.
AU - Steinherz, Laurel
AU - Scheithauer, Berndt
AU - Liu-Mares, W.
AU - Reaman, Gregory H.
PY - 1998/8/15
Y1 - 1998/8/15
N2 - 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 μg/kg/day, starting on Day 7 of each cycle and continuing for at least 7 days, until the absolute neutrophil count was ≤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%).
AB - 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 μg/kg/day, starting on Day 7 of each cycle and continuing for at least 7 days, until the absolute neutrophil count was ≤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%).
KW - Astrocytoma
KW - Brain tumors
KW - Brainstem tumor
KW - Children
KW - Ependymoma
KW - Idarubicin
KW - Medulloblastoma
UR - http://www.scopus.com/inward/record.url?scp=0031812626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031812626&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0142(19980815)83:4<813::AID-CNCR27>3.0.CO;2-U
DO - 10.1002/(SICI)1097-0142(19980815)83:4<813::AID-CNCR27>3.0.CO;2-U
M3 - Article
C2 - 9708950
AN - SCOPUS:0031812626
SN - 0008-543X
VL - 83
SP - 813
EP - 816
JO - Cancer
JF - Cancer
IS - 4
ER -