Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma

BACKGROUND Interleukin-2 (IL-2) has been used widely in the treatment of advanced melanoma, most often using a high dose bolus schedule of administration. We have evaluated the antitumor activity and toxicity of IL-2 when administered by a continuous infusion schedule in patients with metastatic melanoma. METHODS Thirty-three patients with metastatic melanoma were treated with IL-2 using the maximum tolerated dose level of 12 × 106 IU/m2 as a continuous infusion over 24 hours × 4d/week for 4 weeks every 6 weeks. All patients but one had previously received and failed chemotherapy and had evidence of progressive disease. They were required to have normal organ functions and a performance status of 0 to 1. RESULTS We observed 1 complete response and 6 partial responses among 31 evaluable patients for a response rate of 22% (95%, confidence interval: 10% to 41%). The median response duration was 6 months, with a range of 4 to 18 months. The toxicity of IL-2 was severe but manageable on the general inpatient ward. One patient died of hepatic necrosis that was probably related to IL-2. Five patients required dose reduction of IL-2 due to toxicity in the form of hepatic or renal insufficiency, which was rapidly reversible. CONCLUSIONS IL-2, used as a continuous infusion at a dose level of 12 × 106 IU/m2/day, 4 times every week for 4 weeks, has activity against metastatic melanoma similar to that reported with high dose IL-2 given in a bolus schedule. Cancer 1996;77:89-96.