title: A feasibility, toxicity, and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study.
abstract: OBJECTIVE
  The purpose of this study was to determine the feasibility, toxicity, and early response of patients with clinical group III rhabdomyosarcoma (RMS) to a chemotherapy regimen of etoposide (ETOP), ifosfamide (IFOS), and vincristine (VCR) with hyperfractionated radiation therapy (XRT).
  
  
  METHODS
  Sixty-eight patients aged < 21 years, previously untreated, with clinical group III RMS or undifferentiated sarcoma with normal organ function were eligible for this study. Chemotherapy was as follows: weeks 0-8: IFOS 1.8 g/m2/day X 5 days every 3 weeks X 3 (with mesna), ETOP 100 mg/m2/day X 5 days every 3 weeks X 3, and VCR 1.5 mg/m2/week X 9; weeks 9-16: hyperfractionated XRT (except patients with parameningeal tumors with meningeal extension, who received XRT on day 0), IFOS/mesna weeks 9, 12, 16, and VCR weeks 9, 10, 11, 12, 16; weeks 20-99; IFOS/mesna q 3 weeks X 2, ETOP q 3 weeks X 2, and VCR weekly X 6 weeks. Four drug cycles were repeated every 9 weeks, beginning at week 29. In January 1991, the duration of therapy was reduced to 12 courses due to emerging evidence of IFOS-induced renal tubular dysfunction.
  
  
  RESULTS
  Of the 62 patients evaluable for response, 45 (73%) achieved a complete response. There were three fatal toxicities due to infection. Life-threatening neutropenia was seen in 55 of 60 patients, and life-threatening infections occurred in 27 of 60 patients. Twenty-five patients (42%) developed some degree of neurotoxicity from vincristine. Eleven patients (18%) developed nephrotoxicity, 7 cases of which were severe; 6 of the 11 patients who developed nephrotoxicity were < 2 years old.
  
  
  CONCLUSIONS
  This pilot study had toxicity and response rates comparable to the other two Intergroup Rhabdomyosarcoma Study (IRS)-IV pilot trials of vincristine-actinomycin-cyclophosphamide and vincristine-actinomycin-ifosfamide and is, therefore, being evaluated in the current IRS randomized trial. Due to the high incidence of life-threatening neutropenia and infections, the use of growth factors is now routine. Five of 11 patients who developed nephrotoxicity did so after more than eight courses of IFOS; therefore, the current randomized trial limits IFOS to a total of eight courses.
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: C
authors.initials: C
authors.lastname: Arndt
authors.forename: M
authors.initials: M
authors.lastname: Tefft
authors.forename: E
authors.initials: E
authors.lastname: Gehan
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Jenson
authors.forename: M
authors.initials: M
authors.lastname: Link
authors.forename: S
authors.initials: S
authors.lastname: Donaldson
authors.forename: J
authors.initials: J
authors.lastname: Breneman
authors.forename: E
authors.initials: E
authors.lastname: Wiener
authors.forename: B
authors.initials: B
authors.lastname: Webber
authors.forename: H
authors.initials: H
authors.lastname: Maurer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D010865:Pilot Projects; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000532:radiotherapy; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D005047:Etoposide; D007069:Ifosfamide