Hypotonic intrapleural cisplatin chemotherapy as treatment for pleural carcinomatosis in an experimental model

An experimental model of intrapleural (i.pl.) chemotherapy using hypotonic solutions of sodium chloride was developed as a treatment for malignancies in the pleural cavity. In the current study, isotonic (308 mOsm/L), hypotonic (154 mOsm/L) and super-hypotonic (62 mOsm/L) solutions that contained equal amounts of cisplatin (CDDP) were prepared for an evaluation of their therapeutic efficacy and the pharmacokinetics of the drug. After the i.pl. injection of solutions of CDDP into mice with i.pl. tumors, we found that the amount of platinum taken up by tumor cells was significantly higher as the osmolarity of the solution was reduced. Hypotonic conditions continued for 1 hour after i.pl. injection of hypotonic solution. The maximum concentration (Cmax) and the area 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 duration of survival of ddy mice with i.pl. tumors that were given i.pl. CDDP in solutions of lower osmolarity was significantly longer than that of mice given CDDP in an isotonic solution. These results indicate that use of a hypotonic solution might enhance the therapeutic efficacy of CDDP in an experimental model of pleural carcinomatosis. This procedure also seems promising as a prophylactic and therapeutic modality for treatment of patients with i.pl. malignancies.