Phase I/II trial of subcutaneous interleukin-2, granulocyte-macrophage colony-stimulating factor and interferon-α in patients with metastatic renal cell carcinoma

OBJECTIVE To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin-2 (IL-2), interferon-a2b (IFN-a) and granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS Patients with metastatic renal cell carcinoma (RCC) received on a 3 + 3 trial design escalating doses of s. c. GM-CSF, IL-2 and IFN-alpha Dose-limiting toxicities (DLTs) during the first 6-week cycle were used to determine the MTD. A phase II trial was then initiated to determine clinical activity. RESULTS A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). Two DLTs were observed (G3 nausea/ vomiting and fatigue) and the MTD was determined to be GM-CSF 5.0 mu g/ kg/ day, IL2 9.0 mIU/ m 2 / day and IFN-a 5.0 mU/ m 2 / day. Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. The median progression-free survival and overall survival were 6.0 and 23.4 months, respectively. CONCLUSIONS Immunotherapy with concurrent s. c. GMCSF, IL-2 and IFN-a is generally well tolerated. The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients.