title: High-dose carboplatin and recombinant granulocyte-macrophage colony-stimulating factor in advanced-stage recurrent ovarian cancer.
abstract: OBJECTIVE
  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.
  
  
  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 micrograms/kg, 11 at 5 micrograms/kg, 10 at 10 micrograms/kg, and six at 20 micrograms/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 micrograms/kg, debilitating malaise was seen in four of six patients and this was the dose-limiting toxicity. Patient tolerance of the 3-micrograms/kg and 5-micrograms/kg doses was good, but tolerance was limited for the 10-micrograms/kg dose. Febrile neutropenia was seen in four of seven patients at 3 micrograms/kg, two of 11 at 5 micrograms/kg, two of 10 at 10 micrograms/kg, and one of six at 20 micrograms/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%.
  
  
  CONCLUSIONS
  rGM-CSF appears to be effective and tolerable at 5 micrograms/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.
authors.affiliation: Medicine Branch, National Cancer Institute, Bethesda, MD 20892.
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: J
authors.initials: J
authors.lastname: Janik
authors.forename: M A
authors.initials: MA
authors.lastname: Bookman
authors.forename: M
authors.initials: M
authors.lastname: Rothenberg
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: R C
authors.initials: RC
authors.lastname: Young
authors.forename: R F
authors.initials: RF
authors.lastname: Ozols
authors.forename: L
authors.initials: L
authors.lastname: VanderMolen
authors.forename: E
authors.initials: E
authors.lastname: Kohn
authors.forename: J L
authors.initials: JL
authors.lastname: Jacob
mesh_terms: D000328:Adult; D000368:Aged; D001803:Blood Transfusion; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control* / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin