Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma
(2003) In Anti-Cancer Drugs 14(1). p.57-65- Abstract
Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) is studied in a phase I study in the treatment of malignant pleural mesothelioma and pleural thymoma. We studied the pharmacokinetics of doxorubicin and cisplatin used during the HITHOC procedure. Furthermore, the penetration characteristics of doxorubicin were examined. Between 1998 and 2001, 24 perfusions were performed with a solution containing doxorubicin and cisplatin for 90 min at 40-41 degrees C. The dose was first based on square meters body surface, whereas in later studies a fixed concentration of the perfusion fluid was used. Samples of blood and perfusion fluid were collected for doxorubicin and cisplatin measurements. The... (More)
Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) is studied in a phase I study in the treatment of malignant pleural mesothelioma and pleural thymoma. We studied the pharmacokinetics of doxorubicin and cisplatin used during the HITHOC procedure. Furthermore, the penetration characteristics of doxorubicin were examined. Between 1998 and 2001, 24 perfusions were performed with a solution containing doxorubicin and cisplatin for 90 min at 40-41 degrees C. The dose was first based on square meters body surface, whereas in later studies a fixed concentration of the perfusion fluid was used. Samples of blood and perfusion fluid were collected for doxorubicin and cisplatin measurements. The penetration characteristics of doxorubicin in tissue were determined by fluorescence microscopy. The mean AUC(perfusate):AUC(plasma) ratios for doxorubicin and cisplatin (ultrafiltration for plasma) were 99 and 59, respectively. During perfusion the concentration in the perfusate declined essentially according to first-order elimination kinetics for both doxorubicin and cisplatin with half-lives of 74 and 138 min, respectively. At the end of the perfusion, about 35 and 52% of the dose of doxorubicin and cisplatin, respectively, was recovered in the perfusion fluid. One patient developed a nephrotoxicity grade II. No leukopenia or hair loss was seen. Doxorubicin penetrated into the intercostal muscle specimen, albeit that there was considerable variation in distribution throughout the specimen. We conclude that HITHOC with doxorubicin and cisplatin is relatively a safe procedure with the advantage of high intrathoracic cytostatic drug concentrations, while having limited systemic side effects.
(Less)
- author
- van Ruth, S ; van Tellingen, O ; Korse, C M ; Verwaal, V J LU and Zoetmulder, F A N
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- keywords
- Adult, Aged, Analysis of Variance, Area Under Curve, Cisplatin/pharmacokinetics, Doxorubicin/pharmacokinetics, Female, Humans, Hyperthermia, Induced/methods, Intraoperative Care/methods, Male, Mesothelioma/drug therapy, Middle Aged, Pleural Neoplasms/drug therapy, Thoracotomy/methods, Thymoma/drug therapy
- in
- Anti-Cancer Drugs
- volume
- 14
- issue
- 1
- pages
- 57 - 65
- publisher
- Rapid Communications
- external identifiers
-
- scopus:0037265430
- pmid:12544259
- ISSN
- 0959-4973
- DOI
- 10.1097/00001813-200301000-00008
- language
- English
- LU publication?
- no
- additional info
- Copyright 2003 Lippincott Williams & Wilkins
- id
- f02f9b1a-54e1-42d2-ac35-e5ef2f3c5229
- date added to LUP
- 2022-04-12 10:53:20
- date last changed
- 2024-01-08 03:41:43
@article{f02f9b1a-54e1-42d2-ac35-e5ef2f3c5229,
abstract = {{<p>Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) is studied in a phase I study in the treatment of malignant pleural mesothelioma and pleural thymoma. We studied the pharmacokinetics of doxorubicin and cisplatin used during the HITHOC procedure. Furthermore, the penetration characteristics of doxorubicin were examined. Between 1998 and 2001, 24 perfusions were performed with a solution containing doxorubicin and cisplatin for 90 min at 40-41 degrees C. The dose was first based on square meters body surface, whereas in later studies a fixed concentration of the perfusion fluid was used. Samples of blood and perfusion fluid were collected for doxorubicin and cisplatin measurements. The penetration characteristics of doxorubicin in tissue were determined by fluorescence microscopy. The mean AUC(perfusate):AUC(plasma) ratios for doxorubicin and cisplatin (ultrafiltration for plasma) were 99 and 59, respectively. During perfusion the concentration in the perfusate declined essentially according to first-order elimination kinetics for both doxorubicin and cisplatin with half-lives of 74 and 138 min, respectively. At the end of the perfusion, about 35 and 52% of the dose of doxorubicin and cisplatin, respectively, was recovered in the perfusion fluid. One patient developed a nephrotoxicity grade II. No leukopenia or hair loss was seen. Doxorubicin penetrated into the intercostal muscle specimen, albeit that there was considerable variation in distribution throughout the specimen. We conclude that HITHOC with doxorubicin and cisplatin is relatively a safe procedure with the advantage of high intrathoracic cytostatic drug concentrations, while having limited systemic side effects.</p>}},
author = {{van Ruth, S and van Tellingen, O and Korse, C M and Verwaal, V J and Zoetmulder, F A N}},
issn = {{0959-4973}},
keywords = {{Adult; Aged; Analysis of Variance; Area Under Curve; Cisplatin/pharmacokinetics; Doxorubicin/pharmacokinetics; Female; Humans; Hyperthermia, Induced/methods; Intraoperative Care/methods; Male; Mesothelioma/drug therapy; Middle Aged; Pleural Neoplasms/drug therapy; Thoracotomy/methods; Thymoma/drug therapy}},
language = {{eng}},
number = {{1}},
pages = {{57--65}},
publisher = {{Rapid Communications}},
series = {{Anti-Cancer Drugs}},
title = {{Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma}},
url = {{http://dx.doi.org/10.1097/00001813-200301000-00008}},
doi = {{10.1097/00001813-200301000-00008}},
volume = {{14}},
year = {{2003}},
}