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, in whom it appears to have an indirect antitumour effect mediated by increased activity of the host's immune system. A large number of clinical trials (typically noncomparative) have established the efficacy of aldesleukin monotherapy in patients with renal cell carcinoma. Response rates of 13 to 20% achieved after intravenous administration and 18 to 31% after subcutaneous administration are greater than those previously reported ( approximately 10%) for other chemo- and immunotherapeutic agents. Furthermore, many patients who were previously refractory to treatment have achieved stable disease status or better after aldesleukin therapy. Median survival times of at least 37 months have been achieved, and perhaps more encouraging is an isolated report of a 5-year actuarial survival rate of 23%. Bolus intravenous administration of aldesleukin was associated with frequent, and occasionally life-threatening, adverse events. Hypotension and renal, pulmonary and cardiac complications were primarily manifestations of increased vascular permeability. Symptoms were generally manageable with treatment interruption and standard pharmaceutical and/or clinical intervention, although some treatment-related deaths were reported. The severity of adverse events was reduced with continuous infusion of the agent and more substantially so when aldesleukin was administered subcutaneously. In conclusion, despite a lack of comparative and phase III trials, aldesleukin therapy appears to result in a slightly better response rate than those previously reported with other antineoplastic therapies in this difficult-to-treat patient population. Retrospective data indicate that survival duration may be moderately increased by aldesleukin, but further 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 with the potential for reducing adverse events by changing its route of administration, suggest the drug may be a worthwhile therapy for patients with this disease.