Phase I/II study of recombinant interferon alpha and gamma in advanced progressive renal-cell carcinoma

• Published in: Cancer Immunology, Immunotherapy Vol. 31; no. 5; pp. 321 - 324
• Main Authors: de Mulder, P H, Debruyne, F M, Franssen, M P, Geboers, A D, Strijk, S, Reintjes, A G, Doesburg, W H, Damsma, O
• Format: Journal Article
• Language: English
• Published: Germany Springer Berlin Heidelberg 01.09.1990
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - toxicity; Carcinoma, Renal Cell - drug therapy; Drug Evaluation; Female; Humans; Interferon Type I - administration & dosage; Interferon Type I - toxicity; Interferon-gamma - administration & dosage; Interferon-gamma - toxicity; Kidney Neoplasms - drug therapy; Male; Middle Aged; Original; Recombinant Proteins
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/BF01740941

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.