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: 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.
authors.affiliation: NeuroDevelopmental Science Center and The Department of Pediatrics, Children's Hospital Medical Center of Akron, Ohio and Northeast Ohio Medical University, Rootstown, Ohio. Electronic address: bcohen@chmca.org.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Cohen
authors.affiliation: Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, Washington.
authors.forename: J Russell
authors.initials: JR
authors.lastname: Geyer
authors.affiliation: Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
authors.affiliation: Division of Radiology, Phoenix Children's Hospital, Phoenix, Arizona.
authors.forename: John G
authors.initials: JG
authors.lastname: Curran
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, California; Department of Mathematics and Statistics, California State University, Long Beach, California.
authors.forename: Tianni
authors.initials: T
authors.lastname: Zhou
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, California.
authors.forename: Emi
authors.initials: E
authors.lastname: Holmes
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, California.
authors.forename: Sue Ann
authors.initials: SA
authors.lastname: Ingles
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Dunkel
authors.affiliation: Departments of Pediatric Hematology/Oncology/Bone Marrow Transplant, Children's Hospital Colorado and University of Colorado School of Medicine, Denver, Colorado.
authors.forename: Joanne
authors.initials: J
authors.lastname: Hilden
authors.affiliation: Center for Neuroscience and Behavioral Medicine, Children's National Medical Center, Washington, DC.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.affiliation: Division of Pediatric Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.affiliation: Department of Oncology, St. Jude Children' Research Hospital, Memphis, Tennessee.
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.affiliation: Neuro-oncology Program, Division of Hematology, Oncology and BMT, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D060830:Consolidation Chemotherapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D008297:Male; D010865:Pilot Projects; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D002945:Cisplatin
keywords: Children's Oncology Group; high-dose chemotherapy; infant brain tumor; stem-cell support