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Title
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Selective pulmonary artery perfusion followed by blood flow occlusion: new challenge for the treatment of pulmonary malignancies
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Author
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Abstract
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| Introduction: Selective pulmonary artery perfusion (SPAP) is an experimental endovascular technique for the treatment of pulmonary malignancies. This study evaluated blood flow occlusion (BFO) after SPAP and dose-escalation in order to delay washout of gemcitabine from the lung tissue, to augment pulmonary drug exposure and to maintain plasma concentrations equivalent to intravenous administration. Material and methods: Six groups of pigs underwent left-sided SPAP using gemcitabine in a clinically applied dose of 1-1.5g/m(2) after balloon catheterisation. BFO experiment: four groups (n=4, each) were treated with SPAP with 1g/m(2) of gemcitabine during 2 min followed by BFO for 0, 10, 20 and 30 min, respectively. Dose-escalation experiment: two more groups (n=3, each) received SPAP with 1.25 and 1.5g/m(2) Of gemcitabine during 2 min followed by 30 min BFO. All pigs underwent left thoracotomy with sampling of lung, liver and blood. The animals were sacrificed after I h. The lung and plasma areas under the curve (AUC) were calculated for each group and ANOVA and t-test was used for comparison. Results: Thirty minutes BFO resulted in the highest lung AUC compared to 0, 10 and 20 min BFO (p<0.001), while no significant differences in plasma AUC and liver levels were observed. Gemcitabine dose-escalation up to 1.25g/m(2) resulted in significantly higher lung AUC (p=0.02) compared to 1g/m(2), while plasma AUC was equivalent with intravenous treatment. Further dose-escalation to 1.5g/m(2) did not result in significantly higher lung levels compared to 1.25g/m(2). Conclusion: BFO after SPAP delays the washout of gemcitabine from lung tissue. Dose-escalation resulted in higher lung concentrations, while plasma levels were equivalent with intravenous administration. We advocate 2 min of SPAP with 1.25g/m(2) of gemcitabine followed by 30 min of BFO to be investigated as a new treatment modality for pulmonary malignancies. |
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Language
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English
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Source (journal)
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Lung cancer: journal of the International Association for the Study of Lung Cancer / International Association for the Study of Lung Cancer [Aurora, Colo.] - Amsterdam
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Publication
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Amsterdam
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2009
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ISSN
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0169-5002
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DOI
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10.1016/J.LUNGCAN.2008.06.009
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Volume/pages
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63
:3
(2009)
, p. 400-404
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ISI
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000264088700015
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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