A phase II study of the continuous intravenous infusion of interleukin-6 for metastatic renal cell carcinoma.

IL-6 is a pluripotent cytokine with stimulatory effects on megakaryocytes, B lymphocytes, and (in combination with other cytokines) committed hematopoietic stem cells and T cells. IL-6 has direct antitumor activity against murine tumors. We previously completed a Phase I trial of 120-h continuous intravenous infusion of IL-6 repeated every 21 days and found 30 μg/kg/day to be the maximum tolerated dose (MTD), the dosage and schedule used for this Phase II trial. Eligibility requirements included histologic evidence of measurable advanced or metastatic renal cell carcinoma ; no prior immunotherapy for advanced disease ; performance status [PS ; Eastern Cooperative Oncology Group (ECOG)]≤1 ; and adequate hematologic, biochemical, and major organ function compatible with metabolism and safe tolerance of IL-6. Patients received IL-6 at a dosage of 30 μg/kg/day as a 120-h continuous infusion. Courses of therapy were repeated every 21 days. Patients were evaluated for response after every two courses of treatment. Fourteen patients were enrolled in this study : eight men and six women ; ages 34-75 years ; PS 0 :8 patients, PS 1 :6 patients. Twelve patients had prior nephrectomy. Thirty-five courses of IL-6 were administered. Two patients had partial responses of 6 and 8 months' duration (14% response rate ; 95% CI : 2-45%). Eight patients had progressive disease, one patient had a minor response, and three patients had stable disease. Five patients developed atrial fibrillation occurring during the latter half of or soon after completion of the IL-6 infusion. One of these patients developed ischemic abnormalities on electrocardiogram, which resolved spontaneously without evidence of myocardial injury. One patient required electrical cardioversion. One patient required early suspension of treatment with elevation of serum bilirubin, and another developed moderate ataxia of gait. None of the patients experienced thrombocytosis during or after administration of IL-6. Although IL-6 can be administered on this schedule to patients, the modest antitumor activity and unacceptable toxicity of IL-6 of this schedule led to early termination of the study. However, this evidence of antitumor activity suggests that IL-6 should be studied on other schedules and perhaps in combination with other cytokines explored against renal cell carcinoma.