Progressive disease in children with medulloblastoma/PNET during preradiation chemotherapy

The overall prognosis in children with medulloblastoma/PNET has not signifi cantly improved over the past decade. Intensive neoadjuvant chemotherapy ha s not yet adequately explored. We evaluated the short-term clinical results of an intensive chemotherapy regimen in high risk children with newly diag nosed MB/PNET, after surgery and before radiation. Twelve previously untrea ted patients with high-risk medulloblastoma/PNET, according to Chang's clas sification, were treated with the following chemotherapy regimen: high dose carboplatin 600 mg/m(2)/day on days 1 and 2; the same course was administe red 4 weeks later. One month later, high dose cyclophosphamide 2 g/m(2)/day on days 1 and 2, followed by an identical course 4 weeks later. Vincristin e 1, 5 mg/m(2) iv was given on the first day of each course. Systemic evalu ation 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 evalua ted for a residual disease after surgery. After two cycles of high dose car boplatin, 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. O n the other hand, 4 patients clearly showed evidence of PD immediately afte r the first course of cyclophosphamide (2 cases) or following the second co urse. Three of the 4 patients had shown respectively 1 CR and 2 PR after th e second course of carboplatin. Whereas it was confirmed that 2 courses of high dose carboplatin is effective in high risk MB/PNET children, we observ ed an unacceptable number of PD during the subsequent high dose cyclophosph amide 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 chi ldren 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.