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.

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.

Creator

Cohen Bruce H; Geyer J Russell; Miller Douglas C; Curran John G; Zhou Tianni; Holmes Emi; Ingles Sue Ann; Dunkel Ira J; Hilden Joanne; Packer Roger J; Pollack Ian F; Gajjar Amar; Finlay Jonathan L

Publisher

Pediatric neurology

Date

2015
2015-07

Description

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 x 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.

Subject

*Hematopoietic Stem Cell Transplantation/adverse effects; Antineoplastic Agents/administration & dosage/adverse effects; Brain Neoplasms/*therapy; Carboplatin/administration & dosage/adverse effects; Child; Children's Oncology Group; Cisplatin/administration & dosage/adverse effects; Combined Modality Therapy/adverse effects/methods; Consolidation Chemotherapy; Cyclophosphamide/administration & dosage/adverse effects/therapeutic use; Etoposide/administration & dosage/adverse effects; Feasibility Studies; Female; high-dose chemotherapy; Humans; Induction Chemotherapy; Infant; infant brain tumor; Male; Pilot Projects; Preschool; stem-cell support; Thiotepa/administration & dosage/adverse effects; Treatment Outcome; Vincristine/adverse effects/therapeutic use

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

31–46

Issue

1

Volume

53

Citation

Cohen Bruce H; Geyer J Russell; Miller Douglas C; Curran John G; Zhou Tianni; Holmes Emi; Ingles Sue Ann; Dunkel Ira J; Hilden Joanne; Packer Roger J; Pollack Ian F; Gajjar Amar; Finlay Jonathan L, “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.,” NEOMED Bibliography Database, accessed June 13, 2021, https://neomed.omeka.net/items/show/3768.

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