Pharmacokinetics of interleukin-2 in two anephric patients with metastatic renal cell cancer.
BACKGROUND
Most patients with metastatic renal cell carcinoma (RCC) have undergone unilateral- and some bilateral nephrectomy. Because interleukin-2 (IL-2) is thought to be mainly cleared via the kidneys, we investigated whether IL-2 treatment is safe in anephric patients.


METHODS
The pharmacokinetics of i.v. bolus, i.v. infusion and s.c. recombinant IL-2 were investigated in two anephric patients with progressive 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 273 ml/min respectively, were measured in the two patients. In one patient plasma clearance of IL-2 was enhanced to 760 ml/min after continuous i.v. infusion of 4 and 6 million IU IL-2/24 hours, as compared to a clearance of 310 ml/min at a dose of 2 million IU IL-2/24 hours. In the other patient, during 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 dialysates.


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 IL-2 seems feasible.
Schiphorst
P P
PP
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
Chang
P C
PC
Clar
N
N
Schoemaker
R C
RC
Osanto
S
S
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007677:Kidney Function Tests; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D016896:Treatment Outcome
D007376:Interleukin-2