TY - JOUR
T1 - Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma
T2 - Final analysis of Children's Cancer Group Study 9933
AU - MacDonald, Tobey J.
AU - Arenson, Edward B.
AU - Ater, Joann
AU - Sposto, Richard
AU - Bevan, Herbert E.
AU - Bruner, Janet
AU - Deutsch, Melvin
AU - Kurczynski, Elizabeth
AU - Luerssen, Thomas
AU - McGuire-Cullen, Patricia
AU - O'Brien, Richard
AU - Shah, Narayan
AU - Steinbok, Paul
AU - Strain, John
AU - Thomson, John
AU - Holmes, Emi
AU - Vezina, Gilbert
AU - Yates, Allan
AU - Phillips, Peter
AU - Packer, Roger
PY - 2005/12/15
Y1 - 2005/12/15
N2 - BACKGROUND. High-grade astrocytomas (HGA) carry a dismal prognosis and compose nearly 20% of all childhood brain tumors. The role of high-dose chemotherapy (HDCT) in the treatment of HGA remains unclear. METHODS. In a nationwide study, The Children's Cancer Group (CCG) prospectively evaluated 102 children with HGA and postoperative residual disease for efficacy and toxicity of four courses of HDCT before radiotherapy (RT). Patients were randomly assigned to one of three couplets of drugs: carboplatin/etoposide (Regimen A), ifosfamide/etoposide (Regimen B), or cyclophosphamide/etoposide (Regimen C). After HDCT, all patients were to receive local RT followed by lomustine and vincristine. Twenty-six patients were excluded after central neuroradiographic review (n = 8) or pathology review (n = 18). RESULTS. Of 76 evaluable patients (median age, 11.95 yrs; range, 3-20 yrs), 30 patients relapsed during HDCT, and 11 others did not complete HDCT because of toxicity. Nonhematologic serious toxicities were common (29%), and 21% of patients did not receive RT. Objective response rates were not associated with amount of residual disease and did not statistically differ between regimens: 27% (Regimen A), 8% (Regimen B), and 29% (Regimen C). Overall survival (OS) was 24% ± 5% at 5 years and did not differ between groups. Median time to an event was longest for Regimen A (283 days compared with 83 and 91 days for Regimens B and C, respectively). The five-year, event-free survival (EFS) rate for all patients was 8% ± 3% and 14% ± 7% for Regimen A (P = 0.07). CONCLUSIONS. OS and EFS were not affected by histologic grade. Patients who responded to HDCT had a nominally higher survival rate (P = 0.03 for trend). The authors conclude that these commonly used HDCT regimens provide no additional clinical benefit to conventional treatment in HGA, regardless of the amount of measurable residual tumor.
AB - BACKGROUND. High-grade astrocytomas (HGA) carry a dismal prognosis and compose nearly 20% of all childhood brain tumors. The role of high-dose chemotherapy (HDCT) in the treatment of HGA remains unclear. METHODS. In a nationwide study, The Children's Cancer Group (CCG) prospectively evaluated 102 children with HGA and postoperative residual disease for efficacy and toxicity of four courses of HDCT before radiotherapy (RT). Patients were randomly assigned to one of three couplets of drugs: carboplatin/etoposide (Regimen A), ifosfamide/etoposide (Regimen B), or cyclophosphamide/etoposide (Regimen C). After HDCT, all patients were to receive local RT followed by lomustine and vincristine. Twenty-six patients were excluded after central neuroradiographic review (n = 8) or pathology review (n = 18). RESULTS. Of 76 evaluable patients (median age, 11.95 yrs; range, 3-20 yrs), 30 patients relapsed during HDCT, and 11 others did not complete HDCT because of toxicity. Nonhematologic serious toxicities were common (29%), and 21% of patients did not receive RT. Objective response rates were not associated with amount of residual disease and did not statistically differ between regimens: 27% (Regimen A), 8% (Regimen B), and 29% (Regimen C). Overall survival (OS) was 24% ± 5% at 5 years and did not differ between groups. Median time to an event was longest for Regimen A (283 days compared with 83 and 91 days for Regimens B and C, respectively). The five-year, event-free survival (EFS) rate for all patients was 8% ± 3% and 14% ± 7% for Regimen A (P = 0.07). CONCLUSIONS. OS and EFS were not affected by histologic grade. Patients who responded to HDCT had a nominally higher survival rate (P = 0.03 for trend). The authors conclude that these commonly used HDCT regimens provide no additional clinical benefit to conventional treatment in HGA, regardless of the amount of measurable residual tumor.
KW - Children; phase II study
KW - High-dose chemotherapy
KW - High-grade astrocytoma
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U2 - 10.1002/cncr.21593
DO - 10.1002/cncr.21593
M3 - Review article
C2 - 16315242
AN - SCOPUS:29144459136
SN - 0008-543X
VL - 104
SP - 2862
EP - 2871
JO - Cancer
JF - Cancer
IS - 12
ER -