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

Our plain-English summary of Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion, by H. Sakaguchi, H. Ishida, H. Nitanda, et al (Lung Cancer, 2017).

The study

• Authors: H. Sakaguchi, H. Ishida, H. Nitanda, N. Yamazaki, K. Kaneko, K. Kobayashi
• Journal: Lung Cancer
• Published: 2017;104:70-74
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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 © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

In plain English

This open-label prospective study at a Japanese hospital tested a treatment for malignant pleural effusion, fluid build-up in the chest caused by cancer. From August 2005 to March 2008, 20 patients took part: 8 with lung cancer, 7 with pleural mesothelioma and 5 with other cancers. During video-assisted chest surgery, each chest cavity was circulated for one hour with heated saline containing cisplatin at 80 mg/m2. The authors measured total platinum in blood, and total and free (protein-unbound) platinum, which the article calls the drug's active form, in the perfusion fluid. All 20 patients had no pleural effusion 3 months later (95% confidence interval 83 to 100%). On average 33.8 plus or minus 17.0% of the platinum was absorbed into the body; peak blood total platinum was 0.66 plus or minus 0.31 micrograms per mL. Six patients had grade 1 kidney toxicity and 7 had grade 1 vomiting; no grade 2, 3 or 4 toxicities or treatment deaths were observed. The authors concluded that the treatment showed favorable pharmacokinetic profiles as an optional way to control malignant pleural effusion.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: open-label prospective study of pharmacokinetics, safety and effectiveness of a treatment (single treatment group)
• Who was studied: 20 patients with malignant pleural effusion treated at Saitama Medical University International Medical Center, Japan, August 2005 to March 2008: 13 males and 7 females aged 38 to 78; 8 lung cancer (adenocarcinoma), 7 pleural mesothelioma (4 epithelioid, 3 biphasic), 5 other cancers (thymic carcinoma, thymoma, renal cell carcinoma, ovarian carcinoma, unknown primary)
• Exposure: Not an asbestos exposure study. The intervention was intrapleural perfusion with hyperthermic chemotherapy: cisplatin 80 mg/m2 in heated normal saline circulated through the chest cavity for 60 minutes at a pump flow of 1 L/min, under video-assisted thoracoscopic surgery
• Main results:
  • All 20 patients had no pleural effusion 3 months after treatment (95% confidence interval 83 to 100%)
  • Mean systemic absorption rate of total platinum from the pleural space, all patients: 33.8 plus or minus 17.0%
  • Absorption rates were higher in the lung cancer and mesothelioma patients than in patients with other cancers
  • Maximum serum total platinum concentration was 0.66 plus or minus 0.31 micrograms per mL at the end of perfusion. It remained detectable at 0.28 plus or minus 0.12 at 24 hours and 0.21 plus or minus 0.11 at 48 hours
  • Free (protein-unbound) and total platinum in the perfusion solution were measured in only some patients. Free platinum made up 61.1 plus or minus 12.9% of total platinum in the perfusion solution after 1 hour
  • Area under the curve of free platinum in the pleural space was calculated as 26.3 micrograms per mL times hours
  • Side effects: grade 1 renal toxicity in 6 patients and grade 1 emesis in 7 patients. No grade 2 to 4 toxicities and no treatment deaths were observed
• The authors' conclusion: The authors concluded that intrapleural hyperthermic perfusion with cisplatin showed favorable pharmacokinetic profiles as an optional treatment to control malignant pleural effusion. They also described the procedure as safe and effective.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Cisplatin, Pleural Effusion, Prognosis, Performance Status, Video-Assisted Thoracoscopic Surgery (VATS), Lung Cancer, Mesothelioma.

Related studies

• Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies — M. Ried, T. Potzger, et al. (2013)
• Intraoperative hyperthermic chemotherapy perfusion for malignant pleural mesothelioma: an in vitro evaluation — R.B. Cameron, D. Hou (2013)
• Interim results of pleurectomy/decortication and intraoperative intrapleural hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma intolerable to extrapleural pneumonectomy — H. Ishibashi, M. Kobayashi, et al. (2015)
• Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma — S. van Ruth, O. van Tellingen, et al. (2003)
• Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies — V.W. Rusch, D. Niedzwiecki, et al. (1992)
• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)

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