title: Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer.
abstract: BACKGROUND
  This open-label, multicenter, dose-escalation study evaluated multiple dose levels of immunotherapy in patients with metastatic hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, consisted of 2 allogeneic prostate-carcinoma cell lines modified to secrete granulocyte-macrophage-colony-stimulating factor (GM-CSF).
  
  
  METHODS
  Dose levels ranged from 100 x 10(6) cells q28d x 6 to 500 x 10(6) cells prime/300 x 10(6) cells boost q14d x 11. Endpoints included safety, immunogenicity, overall survival, radiologic response, prostate-specific antigen (PSA) kinetics, and serum GM-CSF pharmacokinetics.
  
  
  RESULTS
  Eighty men, median age 69 years (range, 49-90 years), were treated. The most common adverse effect was injection-site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated dose was not established. The median survival time was 35.0 months in the high-dose group, 20.0 months in the mid-dose, group, and 23.1 months in the low-dose group. PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low-dose group, 13 of 18 (72%) in the mid-dose group, and 16 of 18 (89%) in the high-dose group (P = .002; Cochran-Armitage trend test).
  
  
  CONCLUSIONS
  This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway.
authors.affiliation: Department of Oncology, University of Washington Seattle, Seattle, Washington, USA. todd@mclarentodd.com
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: John M
authors.initials: JM
authors.lastname: Corman
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Centeno
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Steidle
authors.forename: Marc
authors.initials: M
authors.lastname: Gittleman
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Simons
authors.forename: Natalie
authors.initials: N
authors.lastname: Sacks
authors.forename: Junko
authors.initials: J
authors.lastname: Aimi
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent; D011471:Prostatic Neoplasms / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor