The overall prognosis in children with
medulloblastoma/
PNET has not significantly improved over the past decade. Intensive
neoadjuvant chemotherapy has not yet adequately explored. We evaluated the short-term clinical results of an intensive
chemotherapy regimen in high risk children with newly diagnosed MB/
PNET, after surgery and before radiation. Twelve previously untreated patients with high-risk
medulloblastoma/
PNET, according to Chang's classification, were treated with the following
chemotherapy regimen: high dose
carboplatin 600 mg/m2/day on days 1 and 2; the same course was administered 4 weeks later. One month later, high dose
cyclophosphamide 2 g/m2/day on days 1 and 2, followed by an identical course 4 weeks later.
Vincristine 1, 5 mg/m2 i.v. was given on the first day of each course. Systemic evaluation of the disease included imaging of the entire neuraxis, including MRI of the entire spine. Out of 12 enrolled, 7 patients were able to be evaluated for a residual disease after surgery. After two cycles of high dose
carboplatin, we noted 1 CR, 4 PR and 2 MR. After the subsequent two cycles of high dose
cyclophosphamide we observed an additional response in 4 cases. On the other hand, 4 patients clearly showed evidence of PD immediately after the first course of
cyclophosphamide (2 cases) or following the second course. Three of the 4 patients had shown respectively 1 CR and 2 PR after the second course of
carboplatin. Whereas it was confirmed that 2 courses of high dose
carboplatin is effective in high risk MB/
PNET children, we observed an unacceptable number of PD during the subsequent high dose
cyclophosphamide therapy. A review from the literature also suggests that, in general, the longer
radiotherapy is delayed, the higher the incidence of PD. In the search for the optimal
drug combination in "sandwich
chemotherapy" for children with high risk MB/
PNET, PD must be reduced to an acceptable incidence, since a high number of PD may significantly lower the probability of long-term survival.