Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: A phase I study

Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses of recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 × 10⁶ C.U./m² (18-72 × 10⁶ I.U./m²) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 × 10⁶ C.U./m², and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 × 10⁶ C.U./m²; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 × 10⁶ C.U./m², 3 of 14 patients (21%) at 6 × 10⁶ C.U./m², and 3 of 6 patients (50%) at 9 × 10⁶ C.U./m². An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 × 10⁶ C.U./m² and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen: