Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion.

OBJECTIVES: Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. METHODS: Patients with MPE, performance status of 0-1, possibility of good lung expansion and Cr<1.2mg/dL were treated with IPHC. The circuit was filled with 2000mL of normal saline containing cisplatin at a dose of 80mg/m2. Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. RESULTS: Twenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3µg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83-100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m2), and the maximum concentration of total platinum in serum was low, 0.66±0.31µg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. CONCLUSIONS: IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.

[Intrapleural perfusion hyperthermo-chemotherapy with cisplatin in patients with malignant pleural mesothelioma].

The preferred treatment for patients with malignant pleural mesothelioma (MPM) has not been determined. In order to obtain adequate control of malignant effusion for multimodality therapy, we have introduced intrapleural perfusion hyperthermo-chemotherapy (IPHC) with cisplatin. IPHC was performed with a roller pump and heat exchanger. Cisplatin was added when the temperature stabilized to a mean of 42.5 degrees C. Dosages of cisplatin were 80 mg/m2. The circuit was filled with 2,000 ml saline. A IPHC was performed for 60 minutes under both lung ventilation. IPHC with cisplatin is feasible, easy to perform, and relatively safe. This method had brought an ideal pleural adhesion. IPHC may offer excellent local control for patients with MPM. Some literatures have reported the utility of IPHC for trimodality therapy on MPM.