Header

UZH-Logo

Maintenance Infos

Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy: a preclinical study


Opitz, I; Erne, B V; Demirbas, S; Jetter, A; Seifert, Burkhardt; Stahel, R; Weder, W (2011). Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy: a preclinical study. Journal of Thoracic and Cardiovascular Surgery, 141(1):65-71.

Abstract

OBJECTIVE: Our objective was to evaluate whether platinum concentrations in chest wall tissue and in serum are optimized by intracavitary application of cisplatin loaded to a fibrin carrier compared with cisplatin solution in a randomized setting of a pig model.

METHODS: After left-sided pneumonectomy including parietal pleurectomy, pigs were randomly assigned to receive either 90 mg/m(2) cisplatin intracavitary solution (n = 6) or to receive 5 mg cisplatin-fibrin (n = 5) applied on a predefined area of the chest wall. Platinum concentration in serum as well as in chest wall tissue was determined at several early time points until day 5 after treatment. Platinum levels were measured by inductively coupled plasma sector field mass spectrometric detection with a matrix-matched calibration procedure.

RESULTS: The dose- and surface-corrected (geometric) mean concentration of cisplatin in chest wall tissue 2 hours but also at day 5 after the application was doubled in animals treated with cisplatin-fibrin compared with the animals treated with cisplatin-solution. In serum, the dose- and surface-corrected exposure toward cisplatin (area under the curve(0-5d)) was significantly lower with cisplatin-fibrin than with cisplatin-solution (P < .0005). This is also reflected by significantly reduced serum creatinine and urea values in the cisplatin-fibrin group (P < .0001). Animals treated with cisplatin-fibrin additionally had a significantly better postoperative course as assessed by a well-being score (P < .001).

CONCLUSIONS: After cisplatin-fibrin treatment, cisplatin tissue concentration was increased whereas systemic cisplatin concentrations were significantly reduced in comparison with cisplatin-solution treatment. This finding offers a clear advantage inasmuch as rate and severity of systemic adverse events can be reduced while local cytotoxic concentrations are at least maintained.

Abstract

OBJECTIVE: Our objective was to evaluate whether platinum concentrations in chest wall tissue and in serum are optimized by intracavitary application of cisplatin loaded to a fibrin carrier compared with cisplatin solution in a randomized setting of a pig model.

METHODS: After left-sided pneumonectomy including parietal pleurectomy, pigs were randomly assigned to receive either 90 mg/m(2) cisplatin intracavitary solution (n = 6) or to receive 5 mg cisplatin-fibrin (n = 5) applied on a predefined area of the chest wall. Platinum concentration in serum as well as in chest wall tissue was determined at several early time points until day 5 after treatment. Platinum levels were measured by inductively coupled plasma sector field mass spectrometric detection with a matrix-matched calibration procedure.

RESULTS: The dose- and surface-corrected (geometric) mean concentration of cisplatin in chest wall tissue 2 hours but also at day 5 after the application was doubled in animals treated with cisplatin-fibrin compared with the animals treated with cisplatin-solution. In serum, the dose- and surface-corrected exposure toward cisplatin (area under the curve(0-5d)) was significantly lower with cisplatin-fibrin than with cisplatin-solution (P < .0005). This is also reflected by significantly reduced serum creatinine and urea values in the cisplatin-fibrin group (P < .0001). Animals treated with cisplatin-fibrin additionally had a significantly better postoperative course as assessed by a well-being score (P < .001).

CONCLUSIONS: After cisplatin-fibrin treatment, cisplatin tissue concentration was increased whereas systemic cisplatin concentrations were significantly reduced in comparison with cisplatin-solution treatment. This finding offers a clear advantage inasmuch as rate and severity of systemic adverse events can be reduced while local cytotoxic concentrations are at least maintained.

Statistics

Citations

Dimensions.ai Metrics
11 citations in Web of Science®
11 citations in Scopus®
8 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

103 downloads since deposited on 23 Mar 2011
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:23 Mar 2011 14:22
Last Modified:17 Feb 2018 13:20
Publisher:Elsevier
ISSN:0022-5223
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jtcvs.2010.09.032
PubMed ID:21168013

Download