HYPOTONIC INTRAPLEURAL CISPLATIN CHEMOTHERAPY AS TREATMENT FOR PLEURAL CARCINOMATOSIS IN AN EXPERIMENTAL-MODEL

An experimental model of intrapleural (i.pl.) chemotherapy using hypot onic solutions of sodium chloride was developed as a treatment for mal ignancies in the pleural cavity. In the current study, isotonic (308 m Osm/L), hypotonic (154 mOsm/L) and super-hypotonic (62 mOsm/L) solutio ns that contained equal amounts of cisplatin (CDDP) were prepared for an evaluation of their therapeutic efficacy and the pharmacokinetics o f the drug. After the i.pl. injection of solutions of CDDP into mice w ith i.pl. tumors, we found that the amount of platinum taken up by tum or cells was significantly higher as the osmolarity of the solution wa s reduced. Hypotonic conditions continued for 1 hour after i.pl. injec tion of hypotonic solution. The maximum concentration (Cmax) and the a rea under the curve of concentration versus time (AUC) for platinum in the plasma was significantly higher in rats given CDDP in a hypotonic solution than in rats given the drug in an isotonic solution. The dur ation of survival of ddy mice with i.pl. tumors that were given i.pl. CDDP in solutions of lower osmolarity was significantly longer than th at of mice given CDDP in an isotonic solution. These results indicate that use of a hypotonic solution might enhance the therapeutic efficac y of CDDP in an experimental model of pleural carcinomatosis. This pro cedure also seems promising as a prophylactic and therapeutic modality for treatment of patients with i.pl. malignancies.