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Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma

The Journal of Thoracic and Cardiovascular Surgery. 2006 Mar;131(3):697-703.e3. Received 2 June 2005;  revised 5 August 2005;  accepted 17 August 2005.  Available online 2 March 2006. [Link]

D. Lardinois MDa, F.J. Jung MDa, I. Opitz MDa, K. Rentsch MDb, C. Latkoczy MDc, V. Vuong PhDd, Z. Varga MDe, V. Rousson PhDf, D. Günther MDc, S. Bodis MDd, R. Stahel MDg and W. Weder MDa

aDivision of Thoracic Surgery, University Hospital, Zurich, Switzerland
bInstitute of Clinical Chemistry, University Hospital, Zurich, Switzerland
dDepartment of Radiation Oncology, University Hospital, Zurich, Switzerland
eInstitute of Clinical Pathology, University Hospital, Zurich, Switzerland
fInstitute of Biostatistics, University Hospital, Zurich, Switzerland
gDivision of Oncology, University Hospital, Zurich, Switzerland
cLaboratory of Inorganic Chemistry, ETH, Zurich, Switzerland

Abstract

Objective: We sought to investigate whether intrapleural topical application of cisplatin with a surgical carrier has a prolonged local tissue level in comparison with cisplatin solution while reducing systemic toxicity.

Methods: Forty immune-competent Fischer rats were inoculated with 106 mesothelioma cells. Ten days later, left pneumonectomy with tumor debulking was performed. Twenty animals underwent local application of cisplatin solution (100 mg/m2), whereas the same quantity of cisplatin was topically applied as a gel with the Vivostat (Vivolution) system in 20 other animals. In each group 5 subgroups of 4 animals were defined according to the harvesting time of blood and tissue samples (2, 4, 24, and 72 hours and 1 week) after local therapy. Platinum concentrations in serum and tissue and systemic toxicity were analyzed.

Results: Platinum concentrations in tissue were significantly higher in the gel group (group 1) than in the solution group (group 2) at 1, 3, and 7 days after therapy (1510, 1224, and 1069 pg/mg for group 1 vs 598, 382, and 287 pg/mg for group 2; P = .007, P = .005, and P = .0002, respectively). Laboratory findings showed renal insufficiency in the animals of the solution group at 1 week, with values of 98 mmol/L versus 7.7 mmol/L for urea and 410 μmol/L versus 43 μmol/L for creatinine (P = .02 and P = .01, respectively), which was confirmed by means of pathologic analysis.

Conclusions: Intrapleural administration of cisplatin with the carrier Vivostat significantly provides sustained higher platinum concentrations up to 1 week in tissue in comparison with application of cisplatin solution without conferring systemic toxicity in this model.

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