title: 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.
abstract: OBJECTIVE
  To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology-Oncology, St. Jude Children's Research Hospital, University of Tennessee, Memphis, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Marina
authors.forename: A S
authors.initials: AS
authors.lastname: Pappo
authors.forename: D M
authors.initials: DM
authors.lastname: Parham
authors.forename: A M
authors.initials: AM
authors.lastname: Cain
authors.forename: B N
authors.initials: BN
authors.lastname: Rao
authors.forename: C A
authors.initials: CA
authors.lastname: Poquette
authors.forename: C B
authors.initials: CB
authors.lastname: Pratt
authors.forename: C
authors.initials: C
authors.lastname: Greenwald
authors.forename: W H
authors.initials: WH
authors.lastname: Meyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide