Failure of granulocyte-macrophage colony-stimulating factor to reduce febrile neutropenia in children with recurrent solid tumors treated with ifosfamide, carboplatin, and etoposide chemotherapy

Authors

  • Neyssa M. Marina MD,

    Corresponding author
    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
    • St. Jude Children's Research Hospital, 332 N. Lauderdale, P.O. Box 318, Memphis, TN, 38101-0318
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  • Sarah J. Shema MS,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • Laura C. Bowman MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • John Rodman Pharm D,

    1. Pharmaceutical Services, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • Edwin C. Douglass MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
    Current affiliation:
    1. St. Christopher's Hospital for Children, Hematology/Oncology Department, Eric Avenue at Front Street, Philadelphia, PA, 19134
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  • Wayne L. Furman MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • Alberto Pappo MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • Victor M. Santana MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • Melissa Hudson MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • William H. Meyer MD,

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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  • Charles B. Pratt MD

    1. Department of Hematology-Oncology, St. Jude Children's Research Hospital, and the Departments of Pediatrics and Clinical Pharmacy, University of Tennessee, College of Medicine, Memphis, Tennessee
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Abstract

Ifosfamide, carboplatin, and etoposide (ICE) chemotherapy has promising activity against various solid tumors but produces significant myelotoxicity that might be ameliorated by hematopoietic growth factors. Twelve patients with relapsed solid tumors were treated with ICE chemotherapy. Carboplatin was given on day 1 at a targeted area under the concentration-time curve (AUC) of 8 mg/mL × min (adjusted for each patient's glomerular filtration rate), followed by ifosfamide 2 g/m2 and etoposide 100 mg/m2 on days 2 through 4. Granulocyte-macrophage colony-stimulating factor (GM-CSF), 1,000 μg/m2/day, was started 24 hours after each course and given for 17 days or until the absolute neutrophil count (ANC) reached 10 × 109/L. Myelotoxicity and responses in these patients were compared to those of eight patients who received the same therapy without GM-CSF. Patients received a median of three courses (range, 1–8). All 20 patients developed grade 4 neutropenia and grade 3 or 4 thrombocytopenia. The median duration of neutropenia was significantly shorter in patients who received GM-CSF (16.75 vs. 10 days, P = 0.005). However, the two groups did not differ in the proportion of courses associated with hospitalization for febrile neutropenia, the duration of hospitalization, or the median duration of thrombocytopenia. There were two complete, four partial, and three objective responses in the 12 patients treated with ICE plus GM-CSF, and two partial and three objective responses in the 8 patients treated with ICE only. GM-CSF did not reduce the occurrence of febrile neutropenia or the duration of thrombocytopenia associated with ICE chemotherapy. Studies of other hematopoietic growth factors in conjunction with this promising combination are merited. © 1994 Wiley-Liss, Inc.

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