A phase II study of subcutaneous recombinant human lnterleukjn-4 in metastatic renal cell carcinoma

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Abstract
Background. A study was conducted to assess the response rate for and toxicity of recombinant human interleukin-4 (IL-4) administered subcutaneously to outpatients with metastutic renal cell cancer. Methods. Human recombinant IL-4 provided by Schering-Plough Research Corporation was administered subcutaneously to 19 patients at a dose of 1 μg/kg three times per week. Eligibility included Cancer and Leukemia Group B performance status of 2 or better, adequate hematologic (leukocyte count ≤2500/μl platelets ≤75,000/μl), renal (creatinine ≤2.0 mg/dl), and hepatic (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase ≤3 times the upper limit of normal) function. Exclusion criteria included prior immunotherapy, clinically significant diabetes, pulmonary disease, and history of congestive heart failure or an ejection fraction of less than 40%. Soluble CD23 was measured in prospectively collected serum via an enzyme-linked immunosorbent assay technique. Results. There was one minor response among 18 evaluable patients and median survival was only 35 weeks. Toxicities included fever, fatigue, myalgias, arthralgias, nausea, and anorexia. One patient each experienced a 14% asymptomatic decrease in the cardiac ejection fraction, a gastrointestinal bleed, and oral angioedema. Ten patients noted increased pain in tumor bearing areas, especially in areas of bony disease. Two patients with pre-existing vertebral disease experienced symptoms of cord compression. In 12 patients for whom complete data were available there was a mean increase in soluble CD23 of 2.6 ng/ml (P = 0.002) 1—2 weeks after therapy initiation. Conclusions. At this modest dose and schedule, IL-4 was tolerated in most patients. There was minimal biologic and clinical activity. Further development of IL-4 as a therapeutic agent in metastatic renal cell cancer at this dose and schedule is not supported by this study. Cancer 1995; 76:1629–33.