Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma

Objective: We sought to investigate whether intrapleural topical application of cisplatin with a surgical carrier has a prolonged local tissue level in comparison with cisplatin solution while reducing systemic toxicity. Methods: Forty immune- competent Fischer rats were inoculated with 106 mesothelioma cells. Ten days later, left pneumonectomy with tumor debulking was performed. Twenty animals underwent local application of cisplatin solution ( 100 mg/m(2)), whereas the same quantity of cisplatin was topically applied as a gel with the Vivostat ( Vivolution) system in 20 other animals. In each group 5 subgroups of 4 animals were defined according to the harvesting time of blood and tissue samples ( 2, 4, 24, and 72 hours and 1 week) after local therapy. Platinum concentrations in serum and tissue and systemic toxicity were analyzed. Results: Platinum concentrations in tissue were significantly higher in the gel group ( group 1) than in the solution group ( group 2) at 1, 3, and 7 days after therapy ( 1510, 1224, and 1069 pg/ mg for group 1 vs 598, 382, and 287 pg/ mg for group 2; P = .007, P = .005, and P = .0002, respectively). Laboratory findings showed renal insufficiency in the animals of the solution group at 1 week, with values of 98 mmol/ L versus 7.7 mmol/ L for urea and 410 mu mol/ L versus 43 mu mol/ L for creatinine ( P = .02 and P = .01, respectively), which was confirmed by means of pathologic analysis. Conclusions: Intrapleural administration of cisplatin with the carrier Vivostat significantly provides sustained higher platinum concentrations up to 1 week in tissue in comparison with application of cisplatin solution without conferring systemic toxicity in this model.