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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

From the Departments of Hematology-Oncology, Pathology and Laboratory Medicine, Surgery, Biostatistics and Epidemiology, and Radiation Oncology, St. Jude Children's Research Hospital; and the Departments of Pediatrics, Pathology, Radiology, and Surgery, University of Tennessee, Memphis, Tennessee.

Address reprint requests to Neyssa M. Marina, MD, Stanford University School of Medicine, Stanford University Medical Center, 300 Pasteur Dr, Stanford, CA 94305-5119.

PURPOSE: To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors.

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 greater 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 time 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 on disease-free survival.

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