title: A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer.
abstract: A recombinant vaccinia virus encoding human prostate-specific antigen (rV-PSA) was administered as three consecutive monthly doses to 33 men with rising PSA levels after radical prostatectomy, radiation therapy, both, or metastatic disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7), and 2.65 x 10(8) plaque forming units. Ten patients who received the highest dose also received 250 microg/m2 granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjunct. No patient experienced any virus-related effects beyond grade I cutaneous toxicity. Pustule formation and/or erythema occurred after the first dose in all 27 men who received > or =2.65 x 10(7) plaque forming units. GM-CSF administration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or without GM-CSF were stable for at least 6 months after primary immunization. Nine patients remained stable for 11-25 months; six of these remain progression free with stable PSA levels. Immunological studies demonstrated a specific T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is safe and can elicit clinical and immune responses, and certain patients remain without evidence of clinical progression for up to 21 months or longer.
authors.affiliation: Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Eder
authors.forename: P W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: K
authors.initials: K
authors.lastname: Roper
authors.forename: G X
authors.initials: GX
authors.lastname: Xu
authors.forename: G J
authors.initials: GJ
authors.lastname: Bubley
authors.forename: J
authors.initials: J
authors.lastname: Boyden
authors.forename: L
authors.initials: L
authors.lastname: Gritz
authors.forename: G
authors.initials: G
authors.lastname: Mazzara
authors.forename: W K
authors.initials: WK
authors.lastname: Oh
authors.forename: P
authors.initials: P
authors.lastname: Arlen
authors.forename: K Y
authors.initials: KY
authors.lastname: Tsang
authors.forename: D
authors.initials: D
authors.lastname: Panicali
authors.forename: J
authors.initials: J
authors.lastname: Schlom
authors.forename: D W
authors.initials: DW
authors.lastname: Kufe
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000187:drug effects; D019496:Cancer Vaccines / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000517:prevention & control*; D013610:Tachycardia / Q000139:chemically induced; D016896:Treatment Outcome; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D004274:DNA, Recombinant; D017430:Prostate-Specific Antigen