title: Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy.
abstract: OBJECTIVE
  The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy.
  
  
  METHODS
  Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B).
  
  
  RESULTS
  The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission.
  
  
  CONCLUSIONS
  This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: T C
authors.initials: TC
authors.lastname: Shea
authors.forename: J R
authors.initials: JR
authors.lastname: Mason
authors.forename: A M
authors.initials: AM
authors.lastname: Storniolo
authors.forename: B
authors.initials: B
authors.lastname: Newton
authors.forename: M
authors.initials: M
authors.lastname: Breslin
authors.forename: M
authors.initials: M
authors.lastname: Mullen
authors.forename: D M
authors.initials: DM
authors.lastname: Ward
authors.forename: L
authors.initials: L
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Christian
authors.forename: R
authors.initials: R
authors.lastname: Taetle
mesh_terms: D000328:Adult; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin