Chemotherapy dose-intensification for pediatric patients with Ewing's family of tumors and desmoplastic small round-cell tumors: A feasibility study at St. Jude Children's Research Hospital

Purpose: To evaluate the feasibility of dose-intensification far patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell rumors. Patients and Methods: From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance. Results Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white, Nineteen patients presented with metastatic disease, 29 had tumors greaser than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and rime to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72% +/- 8% and 60% +/- 9%, respectively. Conclusion: Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact an disease-free survival, J Clin Oncol 17:180-190. (C) 1999 by American Society of Clinical Oncology.