Pharmacokinetics of intraoperative intrapleural cisplatin chemotherapy of various osmolarities in cases of esophageal cancer.

Intraoperative intrapleural (i.pl.) cisplatin (CDDP) treatment during thoracotomy was performed for esophageal cancers. Three patients underwent isotonic (308 mOsm/l) CDDP treatment. Hypotonic CDDP treatments with a 154 mOsm/l solution and a 62 mOsm/l solution were administered to 4 and 9 patients, respectively. The maximum concentrations (Cmax) of both total and filterable platinum in the plasma after injection of the hypotonic solution were significantly higher than those after injection of the isotonic solution. The area under the curve of concentration versus time (AUC) of the plasma of the 62 mOsm/l solution was significantly higher than that of the 154 mOsm/l and isotonic solution. Although higher levels of the Cmax may increase side-effects, the hypotonic condition of the i.pl. fluid and increased AUC in the plasma may escalate the accumulation of platinum in i.pl. cancer cells. These results suggest that hypotonic i.pl. CDDP is tolerable and may be useful for treatment of the incipient phase of pleural carcinomatosis and for prophylaxis of postoperative recurrence.