Pilot study of intensive chemotherapy with peripheral hematopoietic cell support for children less than 3 years of age with malignant brain tumors, the CCG-99703 phase I/II study. A report from the Children's Oncology Group Journal Article


Authors: Cohen, B. H.; Geyer, J. R.; Miller, D. C.; Curran, J. G.; Zhou, T.; Holmes, E.; Ingles, S. A.; Dunkel, I. J.; Hilden, J.; Packer, R. J.; Pollack, I. F.; Gajjar, A.; Finlay, J. L.
Article Title: Pilot study of intensive chemotherapy with peripheral hematopoietic cell support for children less than 3 years of age with malignant brain tumors, the CCG-99703 phase I/II study. A report from the Children's Oncology Group
Abstract: Abstract Background The primary goals of the Children's Cancer Group 99703 study were to assess the feasibility and tolerability of - as well as the response rate to - a novel dose-intensive chemotherapy regimen. Methods Between March 1998 and October 2004, 92 eligible patients were enrolled. Following biopsy/resection, patients received three identical cycles of Induction chemotherapy (vincristine, cyclophosphamide, etoposide, and cisplatin) administered every 21-28 days. Patients without tumor progression then received three consolidation cycles of marrow-ablative chemotherapy (thiotepa and carboplatin) followed by autologous hematopoietic cell rescue. Results The maximum tolerated dose of thiotepa was 10 mg/kg/day × 2 days per cycle. The toxic mortality rate was zero during induction and 2.6% during consolidation. Centrally evaluated response rates to induction and consolidation in evaluable patients with residual tumor were 73.3% and 66.7%, respectively. Disease progression rates on induction and consolidation were 4%. Five-year event-free survival and overall survival were 43.9 ± 5.2% and 63.6 ± 5% respectively. Gross total resection versus less than gross total resection were the only significant outcome comparisons: 5-year maximum tolerated dose and overall survival of 54.4 ± 7% versus 28.9 ± 7% (P = 0.0065) and 75.9 ± 8% versus 48.7 ± 8% (P = 0.0034), respectively. The 5-year maximum tolerated dose for localized (M0) versus metastatic (M1+) medulloblastoma was 67.5 ± 9.5% versus 30 ± 14.5% (P = 0.007). The 5-year maximum tolerated dose and overall survival for desmoplastic medulloblastoma patients versus other medulloblastoma were 78.6 ± 11% versus 50.5 ± 12% (P = 0.038) and 85.7 ± 9.4% versus 60.6 ± 11.6% (P = 0.046), respectively. Conclusions This phase I dose-escalation study of marrow-ablative thiotepa regimen determined a maximum tolerated dose that had acceptable toxicity. Overall survival data justify this strategy for current Children's Oncology Group studies. © 2015 Elsevier Inc.
Keywords: cancer survival; event free survival; cancer surgery; major clinical study; overall survival; disease course; cisplatin; cancer combination chemotherapy; side effect; neurotoxicity; carboplatin; infection; multiple cycle treatment; neutrophil count; phase 2 clinical trial; etoposide; blood toxicity; stomatitis; cyclophosphamide; furosemide; vincristine; continuous infusion; thiotepa; drug fever; pilot study; glioblastoma; medulloblastoma; ependymoma; neuroepithelioma; brain cancer; hyperbilirubinemia; phase 1 clinical trial; children's oncology group; mesna; granulocyte colony stimulating factor; hearing disorder; autologous hematopoietic stem cell transplantation; induction chemotherapy; high-dose chemotherapy; weight change; pontine glioma; uremia; stem-cell support; human; male; female; priority journal; article; infant brain tumor
Journal Title: Pediatric Neurosurgery
Volume: 53
Issue: 1
ISSN: 1016-2291
Publisher: Karger  
Date Published: 2015-07-01
Start Page: 31
End Page: 46
Language: English
DOI: 10.1016/j.pediatrneurol.2015.03.019
PROVIDER: scopus
PUBMED: 26092413
PMCID: PMC5166616
DOI/URL:
Notes: Export Date: 2 July 2015 -- Source: Scopus
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  1. Ira J Dunkel
    255 Dunkel