BIOLOGIC AND CLINICAL EFFECTS OF CONTINUOUS-INFUSION INTERLEUKIN-2 INPATIENTS WITH NONSMALL CELL LUNG-CANCER

Background. Interleukin-2 (IL-2) has shown antitumor activity in some neoplasms, such as melanoma and renal carcinoma, but toxicity derived from bolus administration is significant, particularly at the cardiore spiratory level. Methods. To test feasibility, antitumor activity, pul monary and systemic immunologic effects, and pulmonary function change s of continuous-infusion recombinant IL-2 given to patients with non-s mall cell lung cancer, eleven subjects with Stage III-IV disease were treated in a standard pulmonary medicine unit with a dose of 18 millio n IU/m(2)/day from day 1 to day 13 with 1-day rest on day 7. A second induction course was given after a 3-week rest. In patients with nonpr ogressive disease, four maintenance courses of 6 days' duration at the same dose were planned. Immunologic tests, including lymphocyte pheno type analysis and assays for the detection of tumor necrosis factor (T NF) and of anti-IL-2 antibodies, were performed before and after treat ment in serum and bronchoalveolar lavage fluid (BAL). Cardiopulmonary function tests, including spirometry, arterial blood gas analysis, dif fusion capacity, and echocardiography, were obtained before, during, a nd after treatment. Results. Twenty-one cycles (15 induction courses p lus 6 maintenance courses) were administered. No patient was able to c omplete the six planned courses, and only 3 patients entered the maint enance phase. Reasons for discontinuation included progressive disease in five cases, toxicity in three cases, and patient request in three cases. The most common side effects were fever, hypotension, oliguria, and elevated serum creatinine and liver enzyme levels. No patient req uired intubation or intensive care. No objective response was seen, an d the median survival time was 10 months. Lymphocytosis and eosinophil ia were observed in all patients. Surface marker analysis revealed a s tatistically significant increase in the percentage of CD3+, CD4+, CD2 5+ and DR+ cells in peripheral blood. Lymphoid cells derived from BAL disclosed an increased natural killer activity after IL-2 treatment, a nd TNF was increased in BAL fluid. Pulmonary function tests evidenced an increased alveolar-arterial difference for oxygen allied with a dec rease of forced expiratory volume in 1 second, forced vital capacity, and carbon monoxide transfer coefficient consistent with a significant , albeit not clinically relevant, interstitial lung defect. Conclusion . Continuous-infusion IL-2 is feasible in patients with advanced lung cancer even outside an intensive care unit, but overall compliance is poor. Although clinical pulmonary toxicity is negligible, small but st atistically significant alterations of the pulmonary function are evid ent. In addition, this regimen produces a significant activation of th e immune system at the pulmonary level.