RENAL DYSFUNCTION ASSOCIATED WITH THE ADMINISTRATION OF HIGH-DOSE INTERLEUKIN-2 IN 199 CONSECUTIVE PATIENTS WITH METASTATIC MELANOMA OR RENAL-CARCINOMA

Purpose: To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is curr ently approved) in the treatment of cancer patients. Patients and Meth ods: One hundred ninety-nine consecutive patients with metatstatic ren al carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. Results: Patients receiv ed 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to i ncreased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) appro ximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned t o baseline. Higher peek creatinine values occurred in patients with re nal carcinoma (v melanoma), older patients, males (v females), and tho se who had undergone prior nephrectomy. These same patient subsets rec eived fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyse s showed the appear ance of protein, bilirubin, RBCs, WBCs, and granul ar casts during therapy, which cleared completely on follow-up evaluat ion. Conclusion: High-dose IL-2 can be safely administered to cancer p atients. The associated renal dysfunction is transient and without evi dence of intrinsic long-term renal damage. Practical guidelines for pa tient management have been identified.