[The kinetics of IL-2 after pleural administration in the treatment of neoplastic pleurisy].
The half-life of interleukin-2 (IL-2) is short after intravenous bolus injections (6 to 10 minutes) and elevated doses are necessary for its 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 treatment of neoplastic pleurisy. After a phase one study to determine the maximum tolerated dose (24 x 10(6) IU/m2 per day), we have studied the pharmacokinetics of 21 x 10(6) IU/m2 per day of recombinant IL-2 administered as a continuous intrapleural infusion over 5 days in 6 patients who presented with a neoplastic pleurisy (3 had malignant mesotheliomas and 3 had adeno-carcinomas of unknown primary site). Three patients presented with a partial objective response and no toxic effects beyond grade 2 were noted. Specimens were taken from the pleura and blood following the infusion and were taken at 2, 6, 8, 32, 44, 56, 80 and 120 hours after the end of the infusion. After calibration with IL-2 (Roussel 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 presented with diffuse lesions of the parietal pleura whose initial evaluation included thoracoscopy. The inverse was a patient who was suffering from pleural nodular lesions who had very low pleural levels at the 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Astoul
P
P
Service de Pneumologie, Hôpital de la Conception, Marseille.
Bertault-Peres
P
P
Durand
A
A
Boutin
C
C
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007267:Injections; D007376:Interleukin-2 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000097:blood / Q000473:pathology / Q000628:therapy; D010994:Pleura; D016066:Pleural Effusion, Malignant / Q000378:metabolism; D010997:Pleural Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D010998:Pleurisy / Q000097:blood / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction
D007376:Interleukin-2
Cinétique de l'IL-2 après administration pleurale dans le traitement des pleurésies néoplasiques.