Abstract 394P
Background
The maximum tolerated dose of intravenous (IV) chemotherapy for lung cancer is often limited by systemic toxicities. Selective Pulmonary Artery Perfusion (SPAP) combined with Blood Flow Occlusion (BFO) may increase local drug levels in cell DNA while minimizing systemic exposure. The drug is delivered via a balloon catheter in the pulmonary artery, with blood flowreduced or occluded to prevent washout. Unlike isolated lung perfusion, SPAP-BFO is minimally invasive, allowing for repeated administration. This study compares the pharmacokinetics of gemcitabine (GCB) and its metabolites following SPAP-BFO and IV administration, while evaluating safety.
Methods
Four groups (n=5pigs/group) were treated with GCB (1.25 g/m2): IV for 30 minutes; 10 minutes SPAP without BFO (SPAP-BFO 0%); 10 minutes SPAP-BFO 50% (SPAP-BFO 50%); 10 seconds SPAP followed by complete BFO for 9 minutes and 50 seconds (SPAP-BFO 100%). Concentrations of GCB (dFdC) and metabolites (inactive dFdU, active dFdCTP) were analyzed in plasma and after 30 minutes in lung tissue.
Results
SPAP-BFO is safe, with no physiological effects or acute lung damage. Systemic dFdC exposure increased significantly in both the BFO 0% (vs. IV, p < 0.001; vs. BFO 100%, p < 0.001) and BFO 50% (vs. IV, p < 0.010; vs. BFO 100%, p < 0.010) groups. In the lung, SPAP-BFO 100% exhibited significantly higher dFdCTP exposure than controls (p < 0.010) and BFO 0% (p < 0.050). DNA-bound dFdCTP levels were 4.15 μg/g (BFO 100%) and 4.77 μg/g (BFO 50%), both exceeding the 2.40 μg/g for IV.
Table 394P| Groups | AUC dFdC plasma | AUC dFdCTP lung | Conc. dFdCTP lung (μg/g) |
| lV | 1S04 (1369–1914) | 6.S (6.S-8.2) | 2.40 (1.47-S.72) |
| SPAP-BFO 0% | 272S (2468-S124)a,c | 6.S (6.S-9.2) | 2.69 (1.81-S.80) |
| SPAP-BFO | (2146–2840)a,c | 11.0 (6.70–11.9) | 4.1S (2.46-S.48)a |
| S0% | |||
| SPAP-BFO | 1478 (1411–1810) | S6.4 (21.8–4S.4)a,b | 4.77 (S.21–7.74)a,b |
| 100% |
ap < 0.05 compared to IV
bp < 0.05 compared to SPAP-BFO 0%
cp < 0.05 compared to SPAP-BFO 100%. Values are median (IQR).
Conclusions
This study shows the potential of SPAP-BFO with GCB as therapy for lung cancer, with increased dFdCTP levels in lung tissue for BFO 50% and BFO 100%. Notably, only BFO 100% also reduced systemic exposure, making it the most viable candidate for phase I clinical trials.
Funding
Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society
Disclosure
All authors have declared no conflicts of interest.