title: GM-CSF as a systemic adjuvant in a phase II prostate cancer vaccine trial.
abstract: BACKGROUND
  Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; Leukine [sargramostim], Immunex Corp., Seattle, WA) was administered to a subgroup of 44 patients in a phase II clinical trial for prostate cancer using DC pulsed with HLA-A2-specific prostate-specific membrane antigen (PSMA) peptides. Our purpose was to determine if GM-CSF caused any enhancement of patients' immune responses, including enhancement of clinical response to the DC-peptide treatment. This report compares the clinical responses to DC-peptide infusions with and without systemic GM-CSF treatment.
  
  
  METHODS
  GM-CSF was administered by subcutaneous injection at a dose of 75 microg/m2/day for 7 days with each of six infusion cycles. Prefilled syringes were supplied to the patients for self-administration.
  
  
  RESULTS
  One complete and 8 partial responders were identified among 44 patients who received GM-CSF, as compared to 2 complete and 17 partial responders among 51 patients who did not receive GM-CSF. For patients who received GM-CSF and were tested by delayed-type hypersensitivity (DTH) skin test, 3 cases of improved immune response were identified, compared to 5 cases of improvement in patients who did not receive GM-CSF. The main GM-CSF side effects reported were local reactions at the site of injection, fatigue, pain, and fever. Most reported side effects were of mild severity, with some cases of moderate severity leading to discontinuation of GM-CSF.
  
  
  CONCLUSIONS
  Our results suggest GM-CSF as employed in this trial did not detectably enhance clinical response to DC-peptide infusions, or significantly enhance the measured immune response.
authors.affiliation: Cancer Research Division, Pacific Northwest Cancer Foundation, Northwest Hospital, Seattle, Washington 98125, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Simmons
authors.forename: B A
authors.initials: BA
authors.lastname: Tjoa
authors.forename: M
authors.initials: M
authors.lastname: Rogers
authors.forename: A
authors.initials: A
authors.lastname: Elgamal
authors.forename: G M
authors.initials: GM
authors.lastname: Kenny
authors.forename: H
authors.initials: H
authors.lastname: Ragde
authors.forename: M J
authors.initials: MJ
authors.lastname: Troychak
authors.forename: A L
authors.initials: AL
authors.lastname: Boynton
authors.forename: G P
authors.initials: GP
authors.lastname: Murphy
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D015703:Antigens, CD / Q000008:administration & dosage / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen