TREATMENT OF METASTATIC RENAL-CELL CARCINOMA WITH SUBCUTANEOUS INTERLEUKIN-2 - EVIDENCE FOR NONRENAL CLEARANCE OF CYTOKINES

The circulating cytokine concentrations following administration of su bcutaneous recombinant interleukin 2 (IL-2) in combination with interf eron alpha and 5-fluorouracil used to treat advanced renal cancer were studied. One patient was anephric and on dialysis, and seven had norm al biochemical renal function, although five had undergone single neph rectomy. The pharmacokinetics of IL-2 and changes in IL-6 and tumour n ecrosis factor (TNF)-alpha were essentially similar in all patients in cluding the anephric patient, irrespective of the periods of dialysis, although at some time points, IL-2 concentrations were slightly highe r in the anephric patient than in the others. These results show that for subcutaneous administration of tow-dose IL-2, renal clearance of I L-2 is not important. This contrasts with high-dose, intravenous IL-2 where blood concentrations are higher and renal clearance seems to occ ur, perhaps because of saturation of the non-renal mechanisms of clear ance. The subcutaneous route is certainly preferred if IL-2 is used in -anephric patients and in those with impaired renal function, and it m ay be generally preferred for most purposes.