A phase I study of rDNA alpha-2b interferon as a 6-week continuous intravenous infusion.
Sixteen patients with advanced malignancy were treated with rDNA alpha-2b interferon using a continuous 6-week i.v. schedule. Patients received 1 microgram, 3 mu [corrected], 5 mu and 7 mu/m2/day via a portable infusion pump system, all therapy being on an outpatient basis. The dose-limiting toxicity occurring at 7 mu/m2/day [corrected] was lethargy and somnolence. Five million units (mu) was the maximum tolerated dose but significant nausea, anorexia and lethargy affected 4/5 patients at this level. A dose of 3 mu/m2/day was well tolerated, producing little disturbance of normal activity in the majority of patients. Suppression of WBC and platelets was seen at all doses but was not dose-limiting. There was increasing severity of derangement of hepatic transaminases with increasing dose, and the occurrence of liver toxicity appeared to correlate with nausea, anorexia and lethargy. Assay of serum interferon during the infusion showed that this system maintained a constant level of interferon in the blood. However, the increase did not show a linear pattern with increasing dose, suggesting saturation of metabolic inactivation at 7 mu/m2/day. We recommend that a dose of 3 mu/m2/day be used in future studies of prolonged infusions of alpha-2 interferon.
Smith
D
D
Cancer Research Campaign Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, UK.
Wagstaff
J
J
Thatcher
N
N
Scarffe
H
H
D000328:Adult; D000855:Anorexia / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury; D004341:Drug Evaluation; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous / Q000009:adverse effects; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy; D009325:Nausea / Q000139:chemically induced; D011994:Recombinant Proteins / Q000009:adverse effects
D007370:Interferon Type I; D011994:Recombinant Proteins