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

Carola A.S. Arndt, Mariella Tefft, Edmund Gehan, James Anderson, Michelle Jenson, Michael Link, Sarah Donaldson, John Breneman, Eugene Wiener, Bruce Webber, Harold Maurer

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44 Scopus citations

Abstract

Purpose: 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). Patients and 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 × 5 days every 3 weeks × 3 (with mesna), ETOP 100 mg/m2/day × 5 days every 3 weeks × 3, and VCR 1.5 mg/m2/week × 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 × 2, ETOP q 3 weeks × 2, and VCR weekly × 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.

Original languageEnglish (US)
Pages (from-to)124-129
Number of pages6
JournalAmerican Journal of Pediatric Hematology/Oncology
Volume19
Issue number2
DOIs
StatePublished - Jan 1 1997

Keywords

  • Etoposide
  • Ifosfamide
  • Pilot chemotherapy for rhabdomyosarcoma
  • Rhabdomyosarcoma
  • Vincristine

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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