A study of sequential high dose cyclophosphamide and high dose carboplatin with peripheral stem-cell rescue in resistant or recurrent pediatric brain tumors.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of carboplatin with autologous hematopoietic stem-cell rescue, in children with poor-prognosis brain tumors.


METHODS
A previously determined dose of cyclophosphamide with stem-cell rescue was used as a first course. In a second course, carboplatin was given for 3 days with stem-cell rescue to 20 children. The starting dose of carboplatin was 400 mg/m2/day with increments of 75 mg/m2/day in subsequent cohorts. Toxicity and tumor response were recorded.


RESULTS
There were two grade IV toxicities at the dose level of 775 mg/m2/day. There were no toxic deaths. Thus, the MTD of carboplatin was 700 mg/m2/day for 3 days. There were six complete responses (33%, 95% confidence interval [CI], 13-59%), two partial responses (11%; 95% CI, 1-35%), four with stable diseases (22%; 95% CI, 6-48%) and six progressed (33%; 95% CI, 13-59%) out of 18 assessable. Seven of the eight responses were in primitive neuroectodermal tumors (PNETs) or Germinomas. One child with a metastatic anaplastic astrocytoma had a CR. The median duration of tumor response was 10 months (range: 1.5-87 months) with two children disease free at 66 and 87 months. Actuarial survival is 21%. Median follow-up of survivors is 35 months (range: 15-87 months).


CONCLUSIONS
The MTD of carboplatin with stem-cell rescue is 700 mg/m2/day for 3 days. Sequential stem-cell supported cyclophosphamide and carboplatin was tolerable in children with brain tumors and produced responses in PNETs and Germinomas.
Foreman
N K
NK
The Children's Hospital, Denver, and The University of Colorado, Health Sciences Center, Denver, Colorado 80218, USA. foreman.nicholas@tchden.org
Schissel
D
D
Le
Tuan
T
Strain
J
J
Fleitz
J
J
Quinones
R
R
Giller
R
R
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D016879:Salvage Therapy
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D016190:Carboplatin