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Chemoembolization of lung metastases--pharmacokinetic behaviour of carboplatin in a rat model
Uwe Pohlen1, Hayo Rieger, Bernhard T Meyer
1Department of Surgery, Charité Campus Benjamin Franklin Medical Center, Hindenburgdamm 30, D-12200 Berlin, Germany. Uwe.pohlen@charite.de
Aim:
To improve tumor control in lung metastases using a novel method: unilateral chemoembolization of the lung by instillation of degradable starch microspheres (DSM) and cytotoxic agents via the pulmonal artery.
Materials And Methods:
A rodent model of solitary metastasis (CC531 adenocarcinoma) was studied. The animals were randomized into three groups: the control group receiving carboplatin (45 mg/kg) intravenously, an isolated lung perfusion (ILP) group recieving buffered starch solution and carboplatin (15 mg/kg) and a third group receiving chemoembolization with carboplatin (15 mg/kg) and DSM (2 ml/kg). The total platinum concentration in serum, lung and lung tumor at defined times (15, 30, 60, 120 min) was measured using an inductively coupled plasma mass spectrometer (ICP-MS).
Results:
The area under concentration (AUC) versus time curves showed a 7.9- to 42.6-fold higher concentration in the tumor tissue comparing the ILP and chemoembolization group to the control group (p < 0.01). In the comparison of the AUCs of ILP versus chemoembolization, the tumor tissue of the lung showed a 5.4-fold higher concentration in the chemoembolization group (p < 0.01).
Conclusion:
This is the first study to measure the concentration of carboplatin during chemoembolization of the lung. Compared to intravenous therapy, chemoembolization produced higher tumor tissue concentrations. Comparing chemoembolization to ILP, there was also an increase of carboplatin in the tumor tissue, without histological damage of the surrounding lung parenchyma.
