CARDIOPULMONARY TOXICITY OF TREATMENT WITH HIGH-DOSE INTERLEUKIN-2 IN199 CONSECUTIVE PATIENTS WITH METASTATIC MELANOMA OR RENAL-CELL CARCINOMA

Background. Administration of recombinant interleukin-2 (rIL-2) can me diate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with th e cardiopulmonary toxicity associated with high dose IL-2 therapy is r eviewed. Methods. The treatment courses of all patients receiving high dose intravenous holus rIL-2 from January, 1988, until December, 1992 , were evaluated for cardiopulmonary toxicity. Results. One hundred ni nety-nine patients received 310 courses of treatment. There were no tr eatment-related deaths. Respiratory distress occurred in 3.2% of the c ourses, requiring intubation in one patient. Three obtunded patients w ere endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreat ed and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vas opressors. There were no myocardial infarctions; however, 2.5% of pati ents experienced elevated creatine phosphokinase levels associated wit h elevated MB isoenzymes attributed to cardiac toxicity. Only one of t hese patients developed symptoms. Response rates of 19.6% and 15.7% we re noted in patients with renal cell carcinoma and melanoma, respectiv ely. Hypotension requiring vasopressors was associated with a signific antly improved rate of response in patients with melanoma compared wit h patients not requiring vasopressors (23.2% vs. 6.5%, P-2 = 0.037). C onclusions. Although high dose intravenous rIL-2 therapy can be associ ated with cardiopulmonary toxicity, toxic side effects generally are n ot severe and are rapidly reversible.