title: Phase I study of recombinant beta ser 17 interferon in the treatment of cancer.
abstract: Fifteen patients with advanced malignancy were treated with escalating doses of recombinant beta ser 17 interferon (IFN). Doses ranging from 0.006 to 500 X 10(6) units/m2 were administered according to a dosage escalation scheme by iv push twice weekly (starting 1 week after an initial dose) for a planned minimum of 5 weeks, to be continued as a function of response. Toxic effects were broad in scope but generally low in grade. They included fever, malaise, leukopenia, proteinuria, nausea/vomiting, diarrhea, and mild elevations of serum transaminases and creatinine. In one patient, transient hypotension with bradycardia ensued. Malaise and fever increased somewhat with increasing dose. Doses of up to 500 X 10(6) units/m2 were tolerated without severe toxicity. A maximum tolerated dose was not defined. IFN pharmacokinetics followed a biphasic decay curve, with a distribution phase alpha-half-life of 9 minutes and an elimination phase beta-half-life of 103 minutes. Anti-IFN antibodies by the ELISA technique were present in seven of 15 patients. Presence of antibody did not correlate with toxicity or response. 2',5'-Adenylate synthetase levels were increased 2 and 24 hours after the initial dose, with a trend toward higher increments with higher doses. Minimal anti-tumor responses were seen in two patients with melanoma.
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007674:Kidney Diseases / Q000139:chemically induced; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D007370:Interferon Type I; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase; D000068556:Interferon beta-1a