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Selective Pulmonary Artery Perfusion with Blood Flow Occlusion as a Treatment for Lung Malignancies
Erik Claes1,2, Stijn E Verleden1,2,3, Joke De Raedemaecker1
1ASTARC (Antwerp Surgical Training, Anatomy and Research Centre), University of Antwerp, 2610 Wilrijk, Belgium.
Objective:
Intravenous (i.v.) chemotherapy for lung cancer is limited by systemic toxicities, reducing the maximum tolerated dose. Selective pulmonary artery perfusion (SPAP) with blood flow occlusion (BFO) is an endovascular loco-regional technique developed to increase local drug concentrations in lung tissue while minimizing systemic exposure. This study compares the pharmacokinetics of gemcitabine and its metabolites between SPAP-BFO and i.v. administration while evaluating safety.
Design:
Four groups (5 pigs/group) received gemcitabine (1.25 g/m2): i.v. for 30 min, SPAP-BFO 0% (10 min SPAP without BFO), SPAP-BFO 50% (10 min SPAP with 50% BFO), and SPAP-BFO 100% (10 sec SPAP followed by 9 min 50 sec complete BFO). Concentrations of gemcitabine (2',2'-difluoro-2'-deoxycytidine [dFdC], prodrug) and metabolites (inactive 2',2'-difluoro-2'-deoxyuridine [dFdU], active 2',2'-difluoro-2'-deoxycytidine triphosphate [dFdCTP]) were measured in plasma and after 30 min in lung tissue.
Results:
With SPAP-BFO, no physiological effects nor acute lung damage were observed. Systemic dFdC exposure was significantly higher in the BFO 0% (vs i.v., P < 0.001; vs BFO 100%, P < 0.001) and BFO 50% (vs i.v., P < 0.01; vs BFO 100%, P < 0.01) groups. Lung tissue showed greater dFdCTP exposure with SPAP-BFO 100% over time compared to controls (P < 0.01) and BFO 0% (P < 0.05). At the end of the procedure, mean intracellular dFdCTP concentrations were significantly higher in the BFO 50% (1.43-fold, P < 0.05) and BFO 100% groups (1.95-fold, P < 0.001) compared to i.v.
Conclusions:
SPAP-BFO with gemcitabine is safe and significantly increases dFdCTP lung concentrations. The SPAP-BFO 100% protocol, which enhances lung dFdCTP levels while reducing systemic exposure, shows the greatest potential and warrants further investigation as an endovascular loco-regional treatment for lung cancer.
