GM-CSF as a systemic adjuvant in a phase II prostate cancer vaccine trial

BACKGROUND. Recombinant human granulocyte-macrophage colony-stimulating fac tor (GM-CSF; Leukine(R) [sargramostim], Immunex Corp., Seattle, WA) was adm inistered to a subgroup of 44 patients in a phase II clinical trial for pro state cancer using DC pulsed with HLA-A2-specific prostate-specific membran e antigen (PSMA) peptides. Our purpose was to determine if GM-CSF caused an y enhancement of patients' immune responses, including enhancement of clini cal response to the DC-peptide treatment. This report compares the clinical responses to DC-peptide infusions with and without systemic GM-CSF treatme nt. METHODS. GM-CSF was administered by subcutaneous injection at a dose of 75 mu g/m(2)/day for 7 days with each of six infusion cycles. Prefilled syring es were supplied to the patients for self-administration. RESULTS. One complete and 8 partial responders were identified among 44 pat ients who received GM-CSF, as compared to 2 complete and 17 partial respond ers 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 ef fects reported were local reactions at the site of injection, fatigue, pain , and fever. Most reported side effects were of mild severity, with some ca ses of moderate severity leading to discontinuation of GM-CSF. CONCLUSIONS. Our results suggest GM-CSF as employed in this trial did not d etectably enhance clinical response to DC-peptide infusions, or significant ly enhance the measured immune response. (C) 1999 Wiley-Liss, Inc.