Pharmacokinetic Evaluation of Intrapleural Perfusion with Hyperthermic Chemotherapy using Cisplatin in Patients with Malignant Pleural Effusion

Highlights • Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. Feasible and effective technique is needed, and we have established intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin 80 mg/m2 for 1 hour at 43 °C. • In this study, pharmacokinetic and pharmacodynamics evaluations were performed. • It was found that free-platinum from CDDP in the pleural space under IPHC was very stable compared to that in plasma. We first clarified that AUC of free platinum in the pleural space under IPHC was 26.3 μg/mLxh, which was much higher than 3.47 μg/mLxh when administrating CDDP 80 mg/m2 intravenously. This high AUC value of active form and hyperthermic chemotherapy produced 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 to the body 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.