Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies

Our plain-English summary of Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies, by M. Ried, T. Potzger, N. Braune, et al (Journal of Surgical Oncology, 2013).

The study

• Authors: M. Ried, T. Potzger, N. Braune, C. Diez, R. Neu, Z. Sziklavari, B. Schalke, H.S. Hofmann
• Journal: Journal of Surgical Oncology
• Published: 2013;107(7):735-40
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Assessing the pharmacokinetics of intrapleurally administered cisplatin during hyperthermic intrathoracic chemotherapy perfusion (HITHOC) following pleurectomy/decortication in patients with malignant pleural mesothelioma or advanced thymoma with pleural spread.

Methods: Pharmacokinetic analysis (ICP-MS) of intrapleural cisplatin with a dosage of 100 mg/m(2) (n = 5) or 150 mg/m(2) (n = 5) at 42°C perfusate temperature. Simultaneous pleural perfusion fluid and serum samples were collected at the beginning and every 15 min. Serum samples were collected at the end of the operation, 6, 12, and 24 hr postoperative.

Results: Mean cisplatin levels in the perfusate slightly decreased during the HITHOC. The mean area under the curve ratios (AUC perfusate :AUC serum ) of cisplatin were nearly similar. The mean AUCs of cisplatin in the perfusate were approximately 58 and 55 times greater than detected in the serum. The mean peak of cisplatin in the serum was reached after 1 hr of HITHOC. The AUC of cisplatin in the serum did not significantly differ (P = 0.18) between both groups up to 24 hr after perfusion.

Conclusions: HITHOC with cisplatin provides a pharmacological advantage of high local intrapleural cisplatin concentrations. Elevation of the cisplatin dosage to 150 mg/m(2) did not lead to a significant increase of the systemic cisplatin concentration.

Copyright © 2013 Wiley Periodicals, Inc.

In plain English

This prospective, observational study at one center in Regensburg, Germany, measured concentrations of the cancer drug cisplatin in the chest perfusion fluid and in the blood serum when the drug was given as a one-hour heated chest wash (HITHOC, at 42 degrees C) after surgery to remove the pleura (pleurectomy/decortication). Ten patients treated between June 2010 and April 2012 took part. Five had malignant pleural mesothelioma, and asbestos exposure was evident in three of them. Five had thymoma that had spread to the pleura. The first five patients received 100 mg/m2 of cisplatin and the last five received 150 mg/m2. During the wash, drug exposure in the chest fluid averaged about 58 times (lower dose) and 55 times (higher dose) that in the blood. Blood exposure over 24 hours did not differ significantly between the doses (P = 0.18). No patient died within 30 days. Two patients given the higher dose developed kidney insufficiency, and one needed temporary dialysis. The authors concluded that the method was safe and feasible, and they recommended 150 mg/m2. They named the small sample size as a limitation.

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: Prospective, observational, single-center pharmacokinetic study comparing two cisplatin doses
• Who was studied: 10 patients (7 male, 3 female) treated in a thoracic surgery department in Regensburg, Germany, between June 2010 and April 2012: 5 with malignant pleural mesothelioma (all epithelial type) and 5 with Masaoka stage IVa thymoma with pleural spread. Asbestos exposure was evident in 3 of the 5 mesothelioma patients (60%).
• Exposure: The exposure studied was the drug cisplatin, given into the chest during a 60-minute hyperthermic intrathoracic chemotherapy perfusion at 42 degrees C after pleurectomy/decortication. Group A (first five patients) received 100 mg/m2 and group B (last five patients) received 150 mg/m2. Asbestos exposure was not the subject of the study; the authors only note that it was evident in 3 of the mesothelioma patients.
• Main results:
  • During the 1-hour perfusion, the mean area under the curve (total drug exposure) of cisplatin in the chest perfusion fluid was approximately 58 times (group A, 100 mg/m2) and 55 times (group B, 150 mg/m2) that in the serum.
  • Cisplatin levels in the perfusion fluid declined during the perfusion by approximately 30% in group A and 51% in group B (from 41,200 to 29,000 in group A and from 56,800 to 27,800 in group B, in the units as printed, mg/L).
  • Serum cisplatin peaked after 60 minutes of perfusion in all but two patients, in whom it peaked at 120 minutes. Mean peak serum levels were 930 in group A and 1,302 in group B (units as printed, mg/L).
  • The serum area under the curve up to 24 hours was 53.4 (group A) versus 99.0 (group B), in the units printed (mg/L/min, times 10 to the 4th power). The difference was not statistically significant (P = 0.18); the authors stated that raising the dose to 150 mg/m2 did not significantly increase systemic cisplatin concentration.
  • There were no in-hospital or 30-day deaths among the 10 patients. Major postoperative complications occurred in 3 patients (30%).
  • Two patients treated with 150 mg/m2 developed postoperative renal insufficiency, and one of them required temporary renal replacement therapy. The authors state that none of the patients given 100 mg/m2 had postoperative renal impairment.
• The authors' conclusion: The authors concluded that cytoreductive surgery combined with HITHOC with cisplatin is safe and feasible and gives high local cisplatin concentrations in the chest. They currently recommend 150 mg/m2 and stated that any escalation above this dose should be done carefully because a substantial systemic fraction exists.
• Limitations the authors state:
  • Relatively small sample size
  • Variation between patients in cisplatin concentration in the chest, because the amount of perfusion fluid differed from patient to patient

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Intrathoracic, Chemotherapy, Pleurectomy/Decortication (P/D), Pleural Mesothelioma.

Related studies

• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)
• 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)
• 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)
• Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma — E. de Bree, S. van Ruth, et al. (2002)
• Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy — T. Markowiak, N. Kerner, et al. (2019)
• Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure — M. Ried, K. Lehle, et al. (2015)

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