Pharmacokinetics of Hyperthermic Intrathoracic Chemotherapy following Pleurectomy and Decortication

Our plain-English summary of Pharmacokinetics of Hyperthermic Intrathoracic Chemotherapy following Pleurectomy and Decortication, by P.H. Sugarbaker, O.A. Stuart, C. Eger (Gastroenterology Research and Practice, 2012).

The study

• Authors: P.H. Sugarbaker, O.A. Stuart, C. Eger
• Journal: Gastroenterology Research and Practice
• Published: 2012;2012:471205
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients.

In plain English

This pharmacokinetic study, from MedStar Washington Hospital Center, followed patients whose pseudomyxoma peritonei or peritoneal mesothelioma had spread through the diaphragm into the chest. After surgery to remove the visible tumor in the chest (pleurectomy and decortication), heated chemotherapy containing mitomycin C and doxorubicin was circulated inside the chest, with 5-fluorouracil and leucovorin given by vein. Drug levels in the chest fluid and in the blood were measured every 15 minutes. In the 3 patients whose mitomycin C levels were reported, the drug exposure in the chest fluid was 96 (plus or minus 41) times that in the blood, and about 41 percent of the drug was absorbed into the body. In the 4 patients whose doxorubicin levels were reported, the ratio was 241 (plus or minus 83), and 72 percent was absorbed by 90 minutes. Compared with 25 patients given these drugs in the abdomen, less drug left the chest. The authors concluded that the study gives a strong pharmacologic rationale for regional chemotherapy in this group. The study did not examine asbestos exposure.

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: Pharmacokinetic study of drug levels in patients identified through a prospective clinical database, compared with abdominal (intraperitoneal) chemotherapy data from 25 other patients
• Who was studied: Patients at MedStar Washington Hospital Center whose pseudomyxoma peritonei or peritoneal mesothelioma had extended into the chest through the hemidiaphragm. Mitomycin C levels were reported for 3 patients, all with pseudomyxoma peritonei. Doxorubicin levels were reported for 4 patients: 2 with pseudomyxoma peritonei and 2 with peritoneal mesothelioma. For comparison, 25 patients received the drugs in the abdomen. Study dates were not given.
• Exposure: Heated intrathoracic chemotherapy (HITOC) at 41 to 43 degrees C after pleurectomy and decortication. The chest treatment used mitomycin C 15 mg/m2 and doxorubicin 15 mg/m2 in 2 liters of 1.5% dextrose dialysis solution. 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 were given intravenously. Asbestos exposure was not studied.
• Main results:
  • Mitomycin C, 3 patients: the ratio of drug exposure (area under the curve) in chest fluid to blood was 96 plus or minus 41 over 90 minutes.
  • Mitomycin C: 41 plus or minus 3 percent of the total dose was absorbed from the chest into the body during treatment.
  • About half as much mitomycin C was absorbed from the chest as from the abdomen in the 25 comparison patients. The figure shows about 41% versus about 75% at 90 minutes.
  • Doxorubicin, 4 patients: the chest fluid to blood exposure ratio was 241 plus or minus 83.
  • Doxorubicin: 72 percent was absorbed by 90 minutes when given in the chest, compared with 90 percent in the 25 patients given it in the abdomen.
  • In the discussion, the authors cited unpublished data on 30 treated patients with no recurrences recorded in the chest. Lung complications occurred in 3 of the 30 (10%). Two of these patients developed pulmonary aspergillosis and died.
• The authors' conclusion: The authors concluded that the study provides a strong pharmacologic rationale for regional chemotherapy in these patients. Based on their clinical experience, they judged that further dose escalation does not seem necessary.

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chemotherapy, Peritoneal Mesothelioma, Mitomycin C, Doxorubicin, Thorax.

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)
• Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study — M. Migliore, M. Fiore, et al. (2023)
• Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study — H.H. Elsayed, H.Y. Sharkawy, et al. (2024)
• 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)
• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy, and systemic chemotherapy in patients with malignant pleural mesothelioma: a 10-year experience — L. Lang-Lazdunski, A. Bille, et al. (2015)
• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma — L. Lang-Lazdunski, A. Bille, et al. (2011)

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