PHARMACOKINETICS OF INTRAPLEURAL RECOMBINANT INTERLEUKIN-2 IN IMMUNOTHERAPY FOR MALIGNANT PLEURAL EFFUSION

Citation
P. Astoul et al., PHARMACOKINETICS OF INTRAPLEURAL RECOMBINANT INTERLEUKIN-2 IN IMMUNOTHERAPY FOR MALIGNANT PLEURAL EFFUSION, Cancer, 73(2), 1994, pp. 308-313
Citations number
34
Categorie Soggetti
Oncology
Journal title
CancerACNP
ISSN journal
0008543X
Volume
73
Issue
2
Year of publication
1994
Pages
308 - 313
Database
ISI
SICI code
0008-543X(1994)73:2<308:POIRII>2.0.ZU;2-X
Abstract
Background. The authors measured pharmacokinetic parameters before, du ring, and after immunotherapy by continuous intrapleural infusion of r ecombinant interleukin-2 (rIL-2) and correlated the resulting data wit h clinical effects in nine patients with malignant pleural effusion. M ethods. The underlying disease was malignant mesothelioma in five pati ents and adenocarcinoma in four patients. Continuous intrapleural infu sion of rIL-2 was performed for 5 days at 21 X 10(6) IU/m(2)/day. Maxi mum tolerated dose previously was determined to be 24 X 10(6) IU/m(2)/ day in a Phase I study. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and p lasma samples collected at 0 (baseline), 12, 24, 48, 72, 96, and 120 h ours during infusion and at 2, 6, 8, 32, 44, 56, 80, and 120 hours aft er the end of infusion. Results. High and prolonged intracavitary drug levels were achieved in all but two patients, with a statistically si gnificant correlation between peak values and AUC. Four patients achie ved objective responses according to World Health Organization criteri a. Neither of the patients with undetectable rIL-2 levels had response to therapy. Serum rIL-2 levels were low regardless intrapleural level s. Mean AUC was lower in the plasma than in the pleural fluid. Conclus ions. This study demonstrates that continuous intrapleural infusion of rIL-2 is an active method of treatment for malignant pleural effusion . The low serum levels associated with this method greatly improve tol erance. The results also indicate that the concentration and duration of intrapleural rIL-2 levels may depend on the extent of pleural invas ion. Additional study is needed to confirm this finding.