Interleukin-2-administration intravenously and intrapleurally in a patient with primary pulmonary adenocarcinoma. Cellular responses in peripheral blood,intrapleural fluid and bronchoalveolar lavage

A case report of a patient who suffered from a rapidly progressive lung adenocarcinoma with malignant pleural effusions, is given. The patient failed to respond on two series of conventional cytotoxic drug therapy (Carboplatin, Etoposid). Interleukin-2 (IL-2) treatment was first started as intrapleural instillations (3.0 million IU per day in 6 days). A clear clinical response was achieved with ceasing of the pleural effusion, and the overall disease became stable. In the peripheral blood, there was an increase of CD₄ positive lymphocytes that remained elevated after finishing the installation period. Both in bronchoalveolar lavage (BAL), and in the pleural fluid, there was a marked decrease of cells recovered, possibly due to an enhanced tissue attachment of activated cells. A second analysis with subtyping of lymphocytes in BAL was impossible due to the low cell number. In the pleural fluid, the fractions of CD₃ positive cells increased from 20 to 71% while the ratio between CD₄ and CD₈ remained persistently elevated at 6.11. Because of the disappearance of the pleural effusion, the patient was thereafter treated with IL-2 given as a continuous infusion (18 million IU per square-metre during 24 hours for 5 days). Hereby a more pronounced cell response was achieved in the peripheral blood. In contrast to the intrapleural treatment route, not only CD₄ positive cells, but also the numbers of natural killer cells (NK) increased. However this treatment was also associated with a much higher degree of side effects. It can be concluded from both intrapleural and intravenous IL-2 therapy, that a clinical and immunological response was achieved. As this type of tumour is well known to respond poorly to conventional therapy, treatment with biological modifiers such as IL-2 may offer an interesting alternative in the future.Abbreviations BAL bronchoalveolar lavage - K-2 Interleukin-2     

Intrapleural application of recombinant interleukin-2 in patients with malignant pleurisy due to lung cancer

Forty-three patients with malignant pleurisy due to lung cancer were entered into the trial to evaluate clinical efficacy of intrapleural instillation of recombinant interleukin-2 (RIL-2). Among 35 evaluable patients, serial cytological examinations of pleural effusion following the start of the treatment revealed disappearance of malignant cells in 26 (74%). Malignant cells were detected again in 7 of the 26, however, cytology remained negative in the other 19 patients for longer than 4 weeks. Pleural effusion disappeared roentogenographically in 13 of 35 evaluable patients. Additional 8 patients demonstrated marked decrease of pleural effusion. Complete response (CR) which means disappearance of both malignant cells and pleural effusion for longer than 4 weeks was obtained in 13 of the 35 patients (37%). No serious side effects were experienced in this trial. These results indicate that intrapleural RIL-2 is one of candidates to control intractable malignant pleurisy due to lung cancer.