Anne[a]
Neurooncol. 2005 Jan;71(2):181-187
A study of sequential high dose cyclophosphamide and high dose carboplatin with peripheral stem-cell rescue in resistant or recurrent pediatric brain tumors.
Foreman NK, Schissel D, Le T, Strain J, Fleitz J, Quinones R, Giller R.
The Children´s Hospital, Denver, The University of Colorado, Health Sciences Center, Denver, Colorado, USA.
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 3days with stem-cell rescue to 20 children. The starting dose of carboplatin was 400mg/m(2)/day with increments of 75mg/m(2)/day in subsequent cohorts. Toxicity and tumor response were recorded.
Results:
There were two grade IV toxicities at the dose level of 775mg/m(2)/day. There were no toxic deaths. Thus, the MTD of carboplatin was 700mg/m(2)/day for 3days. 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: 1.5-87months) with two children disease free at 66 and 87months. Actuarial survival is 21%. Median follow-up of survivors is 35months (range: 15-87months).
Conclusion;
The MTD of carboplatin with stem-cell rescue is 700mg/m(2)/day for 3days. Sequential stem-cell supported cyclophosphamide and carboplatin was tolerable in children with brain tumors and produced responses in PNETs and Germinomas.