Feasibility of sequential high-dose chemotherapy and peripheral blood stem cell support for pediatric central nervous system malignancies.
BACKGROUND
The outlook for many brain tumors remains poor. Increased dose intensity has been correlated with response rate and survival in many solid tumors.


METHODS
Ten children with recurrent or newly diagnosed brain tumors were treated with four sequential courses of high-dose single agent chemotherapy with peripheral blood stem cell (PBSC) support. PBSC harvesting was undertaken prior to chemotherapy and following the first course of chemotherapy (3.6 g/m2 etoposide). Each course of chemotherapy consisted of a single drug followed 48 hours later by PBSC reinfusion. Three patients were treated on Regimen A: etoposide, carboplatinum 1.95 g/m2, cyclophosphamide 5 g/m2, and thiotepa 300 mg/m2; three patients were treated on Regimen A' with carmustine 600 mg/m2 replacing cyclophosphamide; four patients received Regimen B: etoposide, carboplatinum 1.95g/m2, cyclophosphamide 7 g/m2, and thiotepa 900 mg/m2.


RESULTS
No course of chemotherapy was complicated by >14 days of neutropenia. Platelet recovery was more prolonged, particularly in patients who had previously received craniospinal irradiation. Non-hematologic toxicity was severe with three toxic deaths including two patients who developed hemolytic-uremic syndrome and respiratory failure. Two of three patients with primitive neuroectodermal tumors had a partial response; no responses were observed in patients with high-grade gliomas.


CONCLUSIONS
Administration of multiple courses of high-dose chemotherapy with PBSC support is feasible in this patient population and successfully mitigates hematologic toxicity. Non-hematologic toxicity becomes prohibitive as chemotherapy doses are escalated.
Jakacki
R I
RI
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indianapolis, IN 46202-5225, USA.
Jamison
C
C
Heifetz
S A
SA
Caldemeyer
K
K
Hanna
M
M
Sender
L
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000532:radiotherapy; D016019:Survival Analysis; D017211:Treatment Failure
D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide