Hirozo Sakaguchi1, H Ishida1, H Nitanda1, N Yamazaki1, K Kaneko1, Kunihiko Kobayashi2. 1. Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan. 2. Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address: kobakuni@saitama-med.ac.jp.
Abstract
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. Copyright Â
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. Copyright Â
Authors: Vittorio Aprile; Diana Bacchin; Stylianos Korasidis; Roberta Ricciardi; Iacopo Petrini; Marcello Carlo Ambrogi; Marco Lucchi Journal: Ann Transl Med Date: 2021-06