Topotecan for the treatment of recurrent or progressive central nervous system tumors - a pediatric oncology group phase II study

Topotecan was studied as a 72 h infusion given every 3 weeks. Treatment beg an at a dose of 1.0 mg/m(2)/day and was increased to 1.25 mg/m(2)/day after the first 6 patients tolerated this higher dose without excessive toxiciti es. Eighty-eight evaluable children were accrued in 6 strata. There were no com plete nor partial responses. Twenty subjects had stable disease (astrocytom a 5/11, malignant glioma 5/13, medulloblastoma 0/12, brain stem tumor 4/19, ependymoma 5/17, and miscellaneous histologies 1/16). Two patients (astroc ytoma, ependymoma) completed the maximum 18 topotecan courses. The remainin g 68 children developed progressive disease within 2 months. Myelosuppression was the main toxicity. Grade 4 leukopenia, neutropenia, an emia, and thrombocytopenia were observed in 18, 32, 5, and 23 participants, respectively. It was concluded that topotecan as given according to this s chedule showed insufficient activity to promote it to frontline protocol us age.