THE KINETICS OF IL-2 AFTER INTRA-PLEURAL ADMINISTRATION IN THE TREATMENT OF NEOPLASTIC PLEURISY

The half-life of interleukine-2 (IL-2) is short after intravenous bolu s injections (6 to 10 minutes) and elevated doses are necessary for it s anti tumour action on account of severe side-effects which limit its use. Studies have shown good tolerance and efficacy of elevated doses of recombinant IL-2 after intrapleural administration in the treatmen t of neoplastic pleurisy. After a phase one study to determine the max imum tolerated dose (24 x 10(6) IU/m2 per day), we have studied the ph armacokinetics of 21 x 10(6) IU/m2 per day of recombinant IL-2 adminis tered as a continuous intrapleural infusion over 5 days in 6 patients who presented with a neoplastic pleurisy (3 had malignant mesothelioma s and 3 had adeno-carcinomas of unknown primary site). Three patients presented with a partial objective response and no toxic effects beyon d grade 2 were noted. Specimens were taken from the pleura and blood f ollowing the infusion and were taken at 2, 6, 8, 32, 44, 56, 80 and 12 0 hours after the end of the infusion. After calibration with IL-2 (Ro ussel Uclaf) the concentrations were assessed using radio-immuno-assay (Amersham). Very elevated pleural levels were obtained for 5 patients with very significant areas under the curve (SSC). All the patients p resented with diffuse lesions of the parietal pleura whose initial eva luation included thoracoscopy. The inverse was a patient who was suffe ring from pleural nodular lesions who had very low pleural levels at t he lower limit of detectability. The blood concentrations were low in all patients and the area under the curve was 1000 times less elevated than for the pleura. These results represent the rationale for using IL-2 by the pleural route and give supporting evidence for the good to lerance and anti-tumoral efficacy of this method of administration. A thoracoscopic evaluation seems essential to assess the pleural lesions and also to select those subjects who are likely to produce a respons e to intrapleural immunotherapy.