ALDESLEUKIN (RECOMBINANT INTERLEUKIN-2) - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES, CLINICAL EFFICACY AND TOLERABILITY IN PATIENTS WITH RENAL-CELL CARCINOMA

Aldesleukin (recombinant interleukin-2), like endogenous interleukin-2 (IL-2), has a variety of immunomodulatory properties. It is currently approved for intravenous use in patients with renal cell carcinoma, i n whom it appears to have an indirect antitumour effect mediated by in creased activity of the host's immune system. A large number of clinic al trials (typically noncomparative) have established the efficacy of aldesleukin monotherapy in patients with renal cell carcinoma. Respons e rates of 13 to 20% achieved after intravenous administration and 18 to 31% after subcutaneous administration are greater than those previo usly reported (perpendicular to 10%) for other chemo- and immunotherap eutic agents. Furthermore, many patients who were previously refractor y to treatment have achieved stable disease status or better after ald esleukin therapy. Median survival times of at least 37 months have bee n achieved and perhaps more encouraging is an isolated report of a 5-y ear actuarial survival rate of 23%. Bolus intravenous administration o f aldesleukin was associated with frequent, and occasionally life-thre atening, adverse events. Hypotension and renal, pulmonary and cardiac complications were primarily manifestations of increased vascular perm eability. Symptoms were generally manageable with treatment interrupti on and standard pharmaceutical and/or clinical intervention, although some treatment-related deaths were reported. The severity of adverse e vents was reduced with continuous infusion of the agent and more subst antially so when aldesleukin was administered subcutaneously. In concl usion, despite a lack of comparative and phase III trials, aldesleukin therapy appears to result in a slightly better response rate than tho se previously reported with other antineoplastic therapies in this dif ficult-to-treat patient population. Retrospective data indicate that s urvival duration may be moderately increased by aldesleukin, but furth er prospective comparative data are required before this may be proven . In view of the poor prognosis associated with renal cell carcinoma, efficacy data from clinical trials evaluating aldesleukin, together wi th the potential for reducing adverse events by changing its route of administration, suggest the drug may be a worthwhile therapy for patie nts with this disease.