Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: Results of a phase II trial

Various cytokine combinations have been tested for efficacy in the treatmen t of metastatic renal cell carcinoma (MRCC). Because several immunologic sy nergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was co nducted on the efficacy and toxicity of subcutaneous, sequentially administ ered, interferon-gamma (IFN gamma), GM-CSF, and IL-2. Fifty-five consecutiv e patients with MRCC were treated with 100 mug recombinant IFN gamma 1b adm inistered thrice weekly during weeks 1 and 4, followed by 400 mug GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients receiv ed 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated eve ry 8 weeks. Five (10%) of patients experienced an objective response (compl ete 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 ph ase II trials with IFN gamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.