title: Sequential Administration of Interferon-gamma, GM-CSF, and Interleukin-2 in Patients With Metastatic Renal Cell Carcinoma: Results of a Phase II Trial.
abstract: SUMMARY: Various cytokine combinations have been tested for efficacy in the treatment of metastatic renal cell carcinoma (MRCC). Because several immunologic synergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was conducted on the efficacy and toxicity of subcutaneous, sequentially administered, interferon-gamma (IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC were treated with 100 &mgr;g recombinant IFNgamma1b administered thrice weekly during weeks 1 and 4, followed by 400 &mgr;g GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated every 8 weeks. Five (10%) of patients experienced an objective response (complete response [CR]: 2%, partial response [PR]: 8%). Fourteen (26%) patients had stable disease with a median duration of 19 months (6-47+). The median overall survival was 12 months (range: 0.3-44 months). No toxicity greater than World Health Organization grade II was observed, with fever (43%) and erythema (43%) being the most frequent side effects. Compared with other phase II trials with IFNgamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.
authors.affiliation: Clinical Division of Oncology and Chair for Medical Experimental Oncology, Department of Medicine I, Department of Urology, University Hospital, and Ludwig Boltzmann Institute for Clinical Experimental Oncology, Vienna, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidinger
authors.forename: Guenther
authors.initials: G
authors.lastname: Steger
authors.forename: Catharina
authors.initials: C
authors.lastname: Wenzel
authors.forename: Gottfried J.
authors.initials: GJ
authors.lastname: Locker
authors.forename: Alexandra C.
authors.initials: AC
authors.lastname: Budinsky
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.forename: Michael
authors.initials: M
authors.lastname: Marberger
authors.forename: Christoph C.
authors.initials: CC
authors.lastname: Zielinski