P. Astoul et al., PHARMACOKINETICS OF INTRAPLEURAL RECOMBINANT INTERLEUKIN-2 IN IMMUNOTHERAPY FOR MALIGNANT PLEURAL EFFUSION, Cancer, 73(2), 1994, pp. 308-313
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.