Sequential Administration of Interferon-gamma, GM-CSF, and Interleukin-2 in Patients With Metastatic Renal Cell Carcinoma: Results of a Phase II Trial.
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.
Schmidinger
Manuela
M
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.
Steger
Guenther
G
Wenzel
Catharina
C
Locker
Gottfried J.
GJ
Budinsky
Alexandra C.
AC
Brodowicz
Thomas
T
Kramer
Gero
G
Marberger
Michael
M
Zielinski
Christoph C.
CC