title: Phase I/II study of recombinant interferon alpha and gamma in advanced progressive renal-cell carcinoma.
abstract: In vitro studies have documented the synergistic antiviral and antiproliferative activity of recombinant interferon alpha (rIFN alpha) and rIFN gamma. Furthermore, rIFN gamma is a strong immunomodulator with optimal effects at a relative low dose (0.1 mg/m2). On the basis of these observations, we began a phase I/II study with the combination of rIFN gamma at 100 micrograms/m2 (2 x 10(6) IU/m2) and rIFN alpha 2c 6 micrograms/m2 (2 x 10(6) IU/m2), injected twice a week subcutaneously. In cases of stable or progressive disease we increased the dose of rIFN alpha 2c every 2 weeks by 6 micrograms/m2 until the maximum tolerated dose was reached. A total of 32 patients with proven progressive renal-cell carcinoma were included. Of the 31 eligible patients, 21 were male and 10 female, their average age was 57.2 years (range 35-72), 28 had had nephrectomy, their median Karnofsky performance status was 90% (70%-100%), and their tumors were localized predominantly to visceral tissue. In 2, response was complete and in 6 it was partial, for a response rate of 25%. The disease had stabilized in 5 patients and progressed in 16. The median duration of partial response was 14 months (8-16 months); of 2 cases of complete response, 1 persists (23+ months), and the other suffered a relapse after 22 months. The median time to response was 24 weeks (18-24 weeks). The maximum tolerated dose of rIFN alpha was 30 micrograms/m2 (range of 6-36 micrograms/m2). Side-effects included those known to be associated with interferon treatment. One patient developed septicemia during a period with grade 4 leukopenia. Our study permits no conclusion regarding the additional value of rIFN gamma.
authors.affiliation: Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: de Mulder
authors.forename: F M
authors.initials: FM
authors.lastname: Debruyne
authors.forename: M P
authors.initials: MP
authors.lastname: Franssen
authors.forename: A D
authors.initials: AD
authors.lastname: Geboers
authors.forename: S
authors.initials: S
authors.lastname: Strijk
authors.forename: A G
authors.initials: AG
authors.lastname: Reintjes
authors.forename: W H
authors.initials: WH
authors.lastname: Doesburg
authors.forename: O
authors.initials: O
authors.lastname: Damsma
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000633:toxicity; D007371:Interferon-gamma / Q000008:administration & dosage / Q000633:toxicity; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma