Pharmacokinetics of interleukin-2 in two anephric patients with metastaticrenal cell cancer

Background: Most patients with metastatic renal cell carcinoma (RCC) have u ndergone unilateral- and some bilateral nephrectomy. Because interleukin-2 (IL-2) is thought to be mainly cleared via the kidneys, we investigated whe ther IL-2 treatment is safe in anephric patients. Patients and methods: The pharmacokinetics of i.v. bolus, i.v. infusion and s.c. recombinant IL-2 were investigated in two anephric patients with prog ressive metastatic RCC. Results: Following i.v. bolus administration of IL-2, plasma half-lives of 126 and 84 minutes respectively, and plasma clearances of 151 ml/min and 27 3 ml/min respectively, were measured in the two patients. In one patient pl asma clearance of IL-2 was enhanced to 760 ml/min after continuous i.v. inf usion of 4 and 6 million IU IL-2/24 hours, as compared to a clearance of 31 0 ml/min at a dose of 2 million IU IL-2/24 hours. In the other patient, dur ing IL-2 infusion of 2, 4 or 6 x 10(6) IU/24 hours, each over the course of 3 days, plasma clearance of IL-2 increased from 311 to 761, and to 687 ml/ min, respectively. IL-2 could not be detected in haemo- or peritoneal dialy sates. Conclusions: IL-2 plasma half-life is only moderately prolonged in anephric patients as compared to patients with normal renal function. Based on our findings, intravenous or subcutaneous treatment of anephric patients with I L-2 seems feasible.