title: Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.
abstract: We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.
authors.affiliation: Department of Urology, General Hospital, Salzburg, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Aulitzky
authors.forename: G
authors.initials: G
authors.lastname: Gastl
authors.forename: W E
authors.initials: WE
authors.lastname: Aulitzky
authors.forename: M
authors.initials: M
authors.lastname: Herold
authors.forename: J
authors.initials: J
authors.lastname: Kemmler
authors.forename: B
authors.initials: B
authors.lastname: Mull
authors.forename: J
authors.initials: J
authors.lastname: Frick
authors.forename: C
authors.initials: C
authors.lastname: Huber
mesh_terms: D000328:Adult; D000368:Aged; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019798:Neopterin; D011994:Recombinant Proteins; D014057:Tomography, X-Ray Computed; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma