INHALED INTERLEUKIN-2 THERAPY IN PULMONARY METASTATIC RENAL-CELL CARCINOMA - 6 YEARS OF EXPERIENCE

PURPOSE Patients with advanced metastatic renal cell carcinoma often c annot or do not want to tolerate high-dose systemic interleukin-2 (IL- 2) therapy and the toxicity associated with it. To reduce toxicity and still maintain or even increase effectiveness, we developed a method to deliver IL-2 locally for the treatment of pulmonary and mediastinal metastases in metastatic renal cell carcinoma patients. PATIENTS AND METHODS We report here 6 years of experience treating 116 metastatic r enal cell carcinoma patients who had pulmonary or mediastinal metastas es with inhaled IL-2. We have utilized three different IL-2 preparatio ns (natural human IL-2 purified from the supernatants of mitogen-activ ated peripheral blood lymphocytes, glycosylated recombinant IL-2 produ ced by Chinese hamster ovary cells, and non-glycosylated recombinant I L-2 produced by bacteria), AU protocols used high-dose inhalation of I L-2, either exclusively (11%), with coadministration of low-dose syste mic IL-2 (33%), or with coadministration of low-dose systemic IL-2 and interferon-alpha (56%). RESULTS Maximal toxicity per total treatment rime was mild (median treatment time, 7.2 months); there was a low inc idence (16%) of World Health Organization grade 3 toxicity. Toxicity a ssociated with exclusive inhalation of IL-2 was local and consisted ma inly of cough. Thus, patients who could not tolerate high-dose systemi c IL-2 were able to tolerate inhalation IL-2 therapy. Progressive pulm onary metastases responded in 15% of patients for a median of 15.5 mon ths (rang, 4.1-33 months) and were stabilized in 55% of patients for a median of 6.6 months (range, 3-51.7 months). The overall response rat e was 16%; disease was stabilized in 49% of patients and disease progr essed in 35% of patients. The overall median response duration was 3.6 months. Median survival was 11.8 months (range, 1.7-68.8 months); exp ected survival according to risk analysis was 5.3 months. CONCLUSIONS Inhalation of IL-2 is a nontoxic and effective treatment for patients with progressive pulmonary and mediastinal metastases. Inhaled IL-2 ef fectively prevented progress of pulmonary metastases in 70% of patient s. Furthermore, patients could be treated as outpatients and remain em ployed. Local administration of IL-2 increases therapeutic effectivene ss with little or no toxicity.