Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion

PurposeWe investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients.MethodsPatients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600mg/m(2) on day one of cycle one, followed by IV as 1000mg/m(2) on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one.ResultsThree male patients (age range 59-68years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. C-max (meanSD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 +/- 0.13, 66.5 +/- 40.6, and 38 +/- 6.27 mu M and following IV infusion, 17 +/- 2.36, 50.8 +/- 3.61, and 83.2 +/- 12.3 mu M, respectively. The AUCinf (mean +/- SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 +/- 1.2, 791.1 +/- 551.2, and 829.9 +/- 217.8 mu Mh and following IV infusion, 12.5 +/- 3.13, 584 +/- 86.6, and 1394.64 +/- 682.2 mu Mh, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia.ConclusionsSystemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.