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

- Intrapleural perfusion with hyperthermic chemotherapy (IPHC) using CDDP 80 mg/m2 for 1 h at 43 °C was developed for malignant pleural effusion.
- In this study, pharmacokinetic and pharmacodynamics evaluations were performed.
- AUC of free platinum in the pleural space was 26.3 μg/mLxh, which was much higher than administrating CDDP 80 mg/m2 intravenously. This high AUC value and hyperthermic chemotherapy produced complete control of pleural effusion for 3 months after IHPC in all cases.
- While, absorption rate of total platinum from the pleural space to the body was 33.8 ± 17.0%, resulting in controllable side effects.

ObjectivesMalignant 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.MethodsPatients with MPE, performance status of 0-1, possibility of good lung expansion and Cr < 1.2 mg/dL were treated with IPHC. The circuit was filled with 2000 mL of normal saline containing cisplatin at a dose of 80 mg/m2. Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1 L/min at a temperature of 43 °C for 1 h. 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.ResultsTwenty 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 26.3 μg/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 ± 13.6 mg/m2), and the maximum concentration of total platinum in serum was low, 0.66 ± 0.31 μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients.ConclusionsIPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.