title: Therapy of advanced prostate cancer with granulocyte macrophage colony-stimulating factor.
abstract: Granulocyte macrophage colony-stimulating factor is a pleiotropic cytokine capable of inducing systemic immune responses against experimental and human tumors. To evaluate the efficacy of GM-CSF treatment in patients with hormone-refractory prostate cancer, we conducted sequential Phase II studies in 36 men with progressive disease after androgen deprivation and antiandrogen withdrawal. In a first cohort of patients (n = 23), GM-CSF was administered s.c. at a dose of 250 microg/m2 daily for 14 days of a 28-day treatment period. After we observed oscillating prostate-specific antigen (PSA) responses in several patients in this first cohort, a second trial was performed in which patients (n = 13) received maintenance GM-CSF (250 microg/m2 three times weekly) after the first 14 days of daily GM-CSF. All patients were treated until disease progression. Response was assessed by evaluation of serial changes in serum PSA and sequential imaging studies. In cohort I, 10 of 22 patients (45%) had a PSA versus time plot with a sawtooth pattern, with PSA declining during GM-CSF therapy and climbing during the off-therapy period; 5 patients had at least two consecutive declines in PSA, with a median response duration of 3.5 months. All but one patient in cohort II experienced a decline in PSA (median decline, 32%), but a PSA decline greater than 50% and sustained for more than 6 weeks was seen in only one patient, who had a >99% decline in PSA and an improvement in bone scan lasting for 14+ months. Changes in PSA levels could not be attributed to direct or indirect effects of GM-CSF on the PSA assay or down-regulation of PSA expression by GM-CSF. Toxicity was very mild, consisting primarily of transient constitutional symptoms and injection site reactions. These data suggest that GM-CSF may have antitumor activity in advanced prostate cancer, and the use of GM-CSF may be a confounding variable when PSA responses are used as an end point in clinical trials evaluating new regimens for the treatment of advanced prostate cancer.
authors.affiliation: Department of Medicine, University of California, San Francisco 94115, USA. eric_small@quickmail.ucsf.edu
authors.forename: E J
authors.initials: EJ
authors.lastname: Small
authors.forename: D M
authors.initials: DM
authors.lastname: Reese
authors.forename: B
authors.initials: B
authors.lastname: Um
authors.forename: S
authors.initials: S
authors.lastname: Whisenant
authors.forename: S C
authors.initials: SC
authors.lastname: Dixon
authors.forename: W D
authors.initials: WD
authors.lastname: Figg
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D015331:Cohort Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen