title: Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer.
abstract: OBJECTIVE
  This trial evaluated the safety, clinical activity, and immunogenicity of an allogeneic cellular immunotherapy in 55 chemotherapy-naïve patients with hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene.
  
  
  METHODS
  HRPC patients with radiologic metastases (n = 34) or rising prostate-specific antigen (PSA) only (n = 21) received a prime dose of 500 million cells and 12 boost doses of either 100 million cells (low dose) or 300 million cells (high dose) biweekly for 6 months. End points were changes in PSA, time to progression, and survival.
  
  
  RESULTS
  Median survival was 26.2 months (95% confidence interval, 17, 36) in the radiologic group: 34.9 months (8, 57) after treatment with the high dose (n = 10) of immunotherapy and 24.0 months (11, 35) with the low dose (n = 24). The median time to bone scan progression in the radiologic group was 5.0 months (2.6, 11.6) with the high dose and 2.8 months (2.8, 5.7) with the low dose. In the rising-PSA group (n = 21) receiving the low dose, the median time to bone scan progression was 5.9 months (5.6, not reached), and median survival was 37.5 months (29, 56). No dose-limiting or autoimmune toxicities were seen; the most common adverse events were injection site reaction and fatigue.
  
  
  CONCLUSIONS
  These results suggest that this GM-CSF-secreting, allogeneic cellular immunotherapy is well tolerated and may have clinical activity in patients with metastatic HRPC. Phase 3 trials to confirm these results are under way.
authors.affiliation: University of California, San Francisco, Comprehensive Cancer Center, San Francisco, California 94115, USA. smalle@medicine.ucsf.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Natalie
authors.initials: N
authors.lastname: Sacks
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: Eugene
authors.initials: E
authors.lastname: Dula
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Centeno
authors.forename: William G
authors.initials: WG
authors.lastname: Nelson
authors.forename: Dale
authors.initials: D
authors.lastname: Ando
authors.forename: Catherine
authors.initials: C
authors.lastname: Howard
authors.forename: Flavia
authors.initials: F
authors.lastname: Borellini
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.forename: Kristen
authors.initials: K
authors.lastname: Hege
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Simons
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen