Phase I trial of interferon gamma retroviral vector administered intratumorally with multiple courses in patients with metastatic melanoma

The purpose of this study was to determine the safety and antitumor activit y of IFN-gamma retroviral vector in patients with advanced melanoma. Sevent een 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 adm inistered at 0.3, 0.5, and 1.0 mi per cohort). No grade III/IV adverse even ts were attributed to study medication. Replication-competent retrovirus wa s not detected in any of the 17 patients by polymerase chain reaction studi es. Eight patients showed elevated anti-tumor antibody responses in compari son with baseline by ELISA. One of nine patients treated with a single cour se 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 ach ieved 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 su ggested in patients with advanced malignancy that received multiple injecti ons.