Pharmacokinetic, angiographic, and histologic comparison of catheter-directed chemoembolization versus systemic chemotherapy in a canine model

Chemotherapy with selective intraarterial embolization may promote sustained contact of the drug with the tumor and thus could be more effective in the treatment. In this phenomenon, pharmacokinetics of a drug such as mitomycin C (MMC) play a significant role in guiding the therapy. Therefore, we have compared the pharmacokinetics of MMC and assessed angiographic, morphologic, and histologic changes in the kidney following intravenous MMC versus renal artery infusion with and without embolization with embolic agents, Rhizoma Bletillae (RE) and Gelfoam (GF). Dogs randomly divided into four groups underwent selective infusion protocols. Blood samples from renal and common iliac veins were analyzed for MMC levels. Angiography and pathology were performed at 4 days. Intravenous MMC (IV-MMC) caused significantly lower renal vein MMC levels than intraarterial MMC (IA-MMC) and GF+MMC. RB+MMC produced the lowest MMC levels in both veins (p <0.05). Common iliac MMC levels were not significantly different after IV-MMC, IA-MMC, or GF+MMC. Angiographic and histologic studies showed extensive bleeding, necrosis, and vasculitis with thrombosis of the target kidneys after RB+MMC, GF+MMC, or IA-MMC, but not IV-MMC. Selective Rhizoma Bletillae chemoembolization can decrease systemic levels of MMC. Gelfoam does not provide sustained local release of MMC or decrease systemic levels of MMC compared with intravenous infusion. Selective renal MMC infusion without an effective embolic agent does not reduce systemic levels compared with intravenous delivery.