Source: Annual Congress 2002 - Isolated lung perfusion and lung cancer

Abstract

Introduction: In order to achieve high lung levels without systemic exposure, isolated lung perfusion (ILuP) is a promising technique for treatment of isolated pulmonary metastases. Toxicity and pharmacokinetics of gemcitabine (GCB) were evaluated in a rat model of ILuP and compared to intravenous (iv) infusion.
Methods: CC531S adenocarcinoma cells were incubated in vitro for 24 hours with GCB. Cell survival was determined 4 days after GCB treatment with the sulforhodamine B test. In a first in vivo experiment, Wag/Rij rats underwent left ILuP with 20mg/kg (n=3), 40mg/kg (n=6), 80mg/kg (n=6), 160mg/kg (n=6), 320mg/kg (n=6) of GCB and a control group (n=6) with buffered starch. After 3 weeks, right pneumonectomy was performed. In addition, survival was determined for rats treated with iv infusion of 40mg/kg (n=10), 80mg/kg (n=10), 160mg/kg (n=10), 320mg/kg (n=6) of GCB and a control group (n=6) with saline (0.09% NaCl). In a second experiment lung and serum GCB levels were determined for rats treated with iv infusion (160mg/kg, n=6) and rats which had ILuP (160mg/kg, n=6; 320 mg/kg, n=6).
Results: Incubation of the CC531S adenocarcinoma cells with GCB led to a 50% decrease (p<0.05) in the number of cells at 24 hours compared to controls at a dose of 21.9 nanoM. After 90 days, the mortality for rats treated with 320mg/kg iv GCB was 100% compared to 17% after ILuP for the same dose. ILuP with 160mg/kg and 320mg/kg resulted in significantly higher lung levels of GCB compared to iv therapy without any systemic leakage.
Conclusion: GCB ILuP is well tolerated to a maximum dose of 320 mg/kg and results in significantly higher GCB lung levels with undetectable serum levels compared to iv treatment.

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B. P. Van Putte, J. M. H. Hendriks, S. Romijn, B. Pauwels, P. E. Y. Van Schil (Edegem, Belgium). Survival and pharmacokinetics of gemcitabine in a rat model of isolated lung perfusion. Eur Respir J 2002; 20: Suppl. 38, 1148

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