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

Study Type – Therapy (individual cohort) Level of Evidence 2b 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‐α2b (IFN‐α) 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‐α. • 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 µg/kg/day, IL‐2 9.0 mIU/m2/day and IFN‐α 5.0 mU/m2/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. GM‐CSF, IL‐2 and IFN‐α 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.