title: Phase I-II trial of interferon-alpha 2b by continuous subcutaneous infusion over 28 days.
abstract: Interferon-alpha 2b (IFN-alpha) was administered by continuous subcutaneous (s.c.) infusion to 23 patients with hematologic malignancies or metastatic solid tumors: 5 patients with multiple myeloma, 3 with malignant melanoma, 2 with chronic myelogenous leukemia (CML), 10 patients with renal cell cancer, and 3 patients with other solid tumors. Drug was delivered by continuous s.c. infusion for 28 days (1 cycle) at daily dose levels of 0.7, 1.4, 2.5, 3.6, or 5.0 X 10(6) IU/m2 to 3, 3, 3, 8, and 6 patients, respectively. At the highest dose level, a severe flu-like syndrome was seen in 3 patients and severe gastrointestinal toxicity in 2 patients. The maximally tolerated dose (MTD) was 3.6 X 10(6) IU/m2.day and the principal toxicity was a mild to moderate flu-like syndrome. Local skin reactions were occasionally noted at all dose levels if the s.c. needle site was not rotated every 3-4 days. At dose levels of 2.5-3.6 X 10(6) IU/m2.day, IFN-alpha serum levels at steady state ranged from 19 to 61 IU/ml. The time to achieve steady-state conditions ranged from 40 to 72 h and at steady state, 24 h area under the concentration time curve (AUC24 h) ranged from 480 to 1,464 IU/ml.h. Objective responses were seen 3 of 17 evaluable patients: 1/7 in renal cell cancer (14%); 1/2 in CML and in one patient with ependymoma. Remissions lasted 4, 8, and 15 months in renal cell, CML, and ependymoma, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Arizona Cancer Center, University of Arizona, Department of Internal Medicine, Tucson 85724.
authors.forename: R T
authors.initials: RT
authors.lastname: Dorr
authors.forename: S E
authors.initials: SE
authors.lastname: Salmon
authors.forename: A
authors.initials: A
authors.lastname: Robertone
authors.forename: E
authors.initials: E
authors.lastname: Bonnem
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007938:Leukemia / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D011994:Recombinant Proteins
chemical_list: D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins