PILOT-STUDY OF SUBCUTANEOUS RECOMBINANT HUMAN INTERLEUKIN-12 IN METASTATIC MELANOMA

The aim of this study was to evaluate the safety profile of s.c. admin istered recombinant human interleukin 12 (rHuIL-12). Pharmacokinetics and pharmacodynamics of rHuIL-12 anti any evidence of antitumor effect were also considered, Ten pretreated patients with progressive metast atic melanoma were enrolled in this pilot study, Patients received a f ixed dose of rHuIL-12 (0.5 mu g/kg) for two identical 28-day cycles, w ith injections given on days 1, 8, and 15 of each cycle, In case of an y evidence of response or disease stabilization, the treatment was con tinued for two further 28-day cycles, Toxicity mainly consisted of a f lu-like syndrome. Transient increases in transaminasemia (6 of 10 pati ents) and triglyceridemia (8 of 10 patients) were observed, Peak serum IL-12 levels were reached 8-12 h after the first injection in all pat ients; no serum IL-12 was detectable in 6 of 9 evaluable patients afte r the last injection of the second cycle, No antibody response to rHuI L-12 could be detected in any of the patients, A marked, transient red uction in circulating CD8(+) and CD16(+) lymphocytes and neutrophils w as observed after the first administration and high levels of serum IF N-gamma and IL-10 were detected in all patients within 24-48 h, Tumor shrinkage, not reaching partial or complete remission, involved the re gression of s.c. nodules (2 of 3 patients), superficial adenopathies ( 1 of 3 patients), and hepatic metastases (1 of 3 patients); regression s were detected after the first cycle of treatment and were maintained in spite of progression at different sites, s.c. rHuIL-12 treatment w as well tolerated and had marked effects on immune parameters and pote ntial antitumor activity.