Fractionated cyclophosphamide and etoposide for children with advanced or refractory solid tumors: A phase II window study

Purpose: Cyclophosphamide (CPA) has a broad spectrum of activity against so lid tumors. Hepatic self-induction of the active metabolite 4-hydroxycyclop hosphamide occurs after repeated administration. We evaluated the clinical efficacy of a window regimen that administers fractionated CPA in conjuncti on with etoposide (VP16) in children with advanced or refractory solid rumo rs. Patients and Methods: Seventeen children with advanced (n = 12) or refracto ry (n = 5) solid tumors were entered onto this phase II window study. The t reatment regimen consisted of intravenous (IV) CPA 500 mg/ m(2)/d and IV VP 16 100 mg/m(2)/d. Both drugs were administered daily by short infusions for 5 consecutive days. Results: A total of 34 courses were administered, with a median of two cour ses per patient. The median interval between chemotherapy courses was 21 da ys (range, 17 to 35 days). Thirty-three courses were assessable for toxicit y, and all patients were assessable for response. No life-threatening toxic ities were observed. The incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%. Fever and neutropenia occurred after 12 of 26 courses without recombinant human granulocyte colony-stimulating factor (r hG-CSF) and after one of eight courses with rhG-CSF (P =.09). Grade 3 or 4 thrombocytopenia occurred after 10 courses (29%). There were no positive bl ood cultures. One heavily pretreated patient developed a localized perirect al abscess that required drainage. There were 10 patients (59%) with partia l responses, four (23.5%) with stable disease, and three with progressive d isease. Conclusion: Fractionated IV CPA and VP16 over 5 days can be safely administ ered in children with advanced or refractory solid tumors and has notable a ntineoplastic activity. J Clin Oncol 18:2576-2581, (C) 2000 by American Soc iety of Clinical Oncology.