High-dose carboplatin and recombinant granulocyte-macrophage colony-stimulating factor in advanced-stage recurrent ovarian cancer

Eddie Reed, John Janik, Michael A. Bookman, Mace Rothenberg, John Smith, Robert C. Young, Robert F. Ozols, Louis Vandermolen, Elise Kohn, Joan L. Jacob, Terri L. Cornelison

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26 Scopus citations

Abstract

Purpose: We investigated whether carboplatin myelosuppression could be favorably modulated by the administration of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in patients with advanced-stage ovarian cancer. Patients and Methods: Thirty-four patients with advanced-stage recurrent ovarian cancer were treated with high-dose carboplatin (800 mg/m2 per 35-day cycle) and rGM-CSF. rGM-CSF was administered as a daily subcutaneous injection starting 72 hours after the carboplatin dose and continuing until 7 days beyond the WBC nadir. rGM-CSF was administered in a phase I fashion. Seven patients were treated at an rGM-CSF dose of 3 μg/kg, 11 at 5 μg/kg, 10 at 10 μg/kg, and six at 20 μg/kg. Results: rGM-CSF-related toxicities that were not dose-related included nonneutropenic fever, rib pain, acute hypersensitivity reaction, and pericarditis. At the rGM-CSF dose of 20 μg/kg, debilitating malaise was seen in four of six patients and this was the dose-limiting tox-icity. Patient tolerance of the 3-μg/kg and 5-μg/kg doses was good, but tolerance was limited for the 10-μg/kg dose. Febrile neutropenia was seen in four of seven patients at 3 μg/kg, two of 11 at 5 μg/kg, two of 10 at 10 μg/kg, and one of six at 20 μg/kg. Cumulative carboplatin myelotoxicity was blunted only in respect to WBC count, and not for platelets or RBCs. Gastrointestinal bleeding was seen in seven patients. The administered dose-intensity of carboplatin averaged 134 mg/m2/wk for the cohort, or 670 mg/m2 per 35-day cycle. There were two clinical complete responses and eleven partial responses, for a response rate of 38%. Conclusion: rGM-CSF appears to be effective and tolerable at 5 μg/kg/d administered subcutaneously, if given with carboplatin doses up to approximately 600 mg/m2 over 35 days. The use of rGM-CSF with high-dose carboplatin is associated with a substantial response rate in poor-prognosis ovarian cancer patients.

Original languageEnglish (US)
Pages (from-to)2118-2126
Number of pages9
JournalJournal of Clinical Oncology
Volume11
Issue number11
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Reed, E., Janik, J., Bookman, M. A., Rothenberg, M., Smith, J., Young, R. C., Ozols, R. F., Vandermolen, L., Kohn, E., Jacob, J. L., & Cornelison, T. L. (1993). High-dose carboplatin and recombinant granulocyte-macrophage colony-stimulating factor in advanced-stage recurrent ovarian cancer. Journal of Clinical Oncology, 11(11), 2118-2126. https://doi.org/10.1200/JCO.1993.11.11.2118