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

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.

• Authors: Hirozo Sakaguchi, H Ishida, H Nitanda, N Yamazaki, K Kaneko, Kunihiko Kobayashi
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 104 Pg. 70-74 (02 2017) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 28213004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Platinum
• Cisplatin

Topics

• Adult
• Aged
• Cisplatin (administration & dosage, adverse effects, pharmacokinetics, pharmacology)
• Female
• Humans
• Hyperthermia, Induced (adverse effects, methods)
• Infusions, Intralesional (adverse effects, instrumentation)
• Lung Neoplasms (complications, drug therapy, pathology, surgery)
• Male
• Mesothelioma (drug therapy)
• Middle Aged
• Perfusion (adverse effects, methods)
• Platinum (therapeutic use)
• Pleural Cavity (drug effects)
• Pleural Effusion, Malignant (drug therapy, pathology)
• Pleural Neoplasms (drug therapy)
• Prospective Studies
• Thoracic Surgery, Video-Assisted (methods)