title: Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.
authors.affiliation: Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Hirozo
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nitanda
authors.affiliation: Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamazaki
authors.affiliation: Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of General Thoracic Surgery, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address: kobakuni@saitama-med.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods*; D036502:Infusions, Intralesional / Q000009:adverse effects / Q000295:instrumentation; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy; D008875:Middle Aged; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D010984:Platinum / Q000627:therapeutic use; D035422:Pleural Cavity / Q000187:drug effects*; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000473:pathology; D010997:Pleural Neoplasms / Q000188:drug therapy; D011446:Prospective Studies; D020775:Thoracic Surgery, Video-Assisted / Q000379:methods*
chemical_list: D010984:Platinum; D002945:Cisplatin
keywords: Cisplatin; Intrapleural perfusion with hyperthermic chemotherapy; Lung cancer; Mesothelioma; Pharmacokinetics