Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 71, Issue 2, Pages 181-187Publisher
SPRINGER
DOI: 10.1007/s11060-004-1366-2
Keywords
carboplatin; high dose therapy; pediatric
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Purpose: To determine the maximum tolerated dose (MTD) of carboplatin with autologous hematopoietic stem- cell rescue, in children with poor- prognosis brain tumors. Patients and 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/m(2)/day with increments of 75 mg/m(2)/day in subsequent cohorts. Toxicity and tumor response were recorded. Results: There were two grade IV toxicities at the dose level of 775 mg/m(2)/day. There were no toxic deaths. Thus, the MTD of carboplatin was 700 mg/m(2)/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). Conclusion: The MTD of carboplatin with stem-cell rescue is 700 mg/m(2)/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.
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