title: Phase I trial of interferon gamma retroviral vector administered intratumorally with multiple courses in patients with metastatic melanoma.
abstract: The purpose of this study was to determine the safety and antitumor activity of IFN-gamma retroviral vector in patients with advanced melanoma. Seventeen patients (9 single courses, 8 multiple courses) received a total of 363 intratumor injections of IFN-gamma retroviral vector (1 x 10(7) PFU/ml administered at 0.3, 0.5, and 1.0 ml per cohort). No grade III/IV adverse events were attributed to study medication. Replication-competent retrovirus was not detected in any of the 17 patients by polymerase chain reaction studies. Eight patients showed elevated anti-tumor antibody responses in comparison with baseline by ELISA. One of nine patients treated with a single course had an optimal response of stable disease, compared with eight of eight multiple-injected patients. Median survival of single-injected patients was 150 days, and patients who received multiple injections have still not achieved median survival duration, with four of eight still living (p = 0.0462, Wilcoxon; p = 0.0273, log rank). We conclude that intratumor injection of IFN-gamma is safe and well tolerated. Evidence of antitumor activity is suggested in patients with advanced malignancy that received multiple injections.
authors.affiliation: PRN Research, Inc., Dallas, TX 75246, USA. JJNemun@PRNINC.com
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: T
authors.initials: T
authors.lastname: Fong
authors.forename: F
authors.initials: F
authors.lastname: Burrows
authors.forename: J
authors.initials: J
authors.lastname: Bruce
authors.forename: G
authors.initials: G
authors.lastname: Peters
authors.forename: N
authors.initials: N
authors.lastname: Ognoskie
authors.forename: W
authors.initials: W
authors.lastname: Meyer
authors.forename: D
authors.initials: D
authors.lastname: Wynne
authors.forename: R
authors.initials: R
authors.lastname: Kerr
authors.forename: J
authors.initials: J
authors.lastname: Pippen
authors.forename: F
authors.initials: F
authors.lastname: Oldham
authors.forename: D
authors.initials: D
authors.lastname: Ando
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007267:Injections; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D008979:Moloney murine leukemia virus; D014407:Tumor Cells, Cultured
chemical_list: D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007371:Interferon-gamma