PHASE-II STUDY OF DAILY ORAL ETOPOSIDE IN CHILDREN WITH RECURRENT BRAIN-TUMORS AND OTHER SOLID TUMORS

Pre-clinical data and adult experience suggests that topoisomerase tar geted anti-cancer agents may be highly schedule dependent, and efficac y may improve with prolonged exposure. To investigate this hypothesis, 28 children with recurrent brain and solid tumors were enrolled in a phase II study of oral etoposide (ETP). Patients were prescribed ETP a t 50 mg/m(2)/day for 21 consecutive class. Courses were repeated every 28 days pending bone marrow recovery. Evaluation oi response was init ially performed after 8 weeks and then every 12 weeks either by CT or MRI. Three of 4 patients with PNET (primitive neuroectodermal tumor)/m edulloblastora achieved a partial response (PR). Two of 5 with ependym oma responded, one with a complete response and one with a PR. Toxicit y was manageable with only 1 admission for lever and neutropenia in 12 0 cycles of therapy. Five patients had grade 3 or 4 neutropenia. One h ad grade 4 thrombocytopenia and one grade 2 mucositis and withdrew as a result. One patient had grade 2 diarrhea. Two patients who achieved a PR had received ETP as part of prior combination chemotherapy regime ns. Daily oral etoposide is active in recurrent PNET/medulloblastoma a nd ependymoma. Toxicity is manageable and rarely requires intervention . Daily oral etoposide in combination with crosslinking agents should be considered in future phase III trials. Determination of activity in glioma and solid tumors is not complete. (C) 1997 Wiley-Liss, Inc.