Pharmacokinetics of a retrograde infusion of Paclitaxel into the thoracic duct in a porcine model

Gastrointestinal cancer with massive nodal metastases is a lethal disease. In this study, using a porcine model, we attempted to infuse the anti-cancer drug, Paclitaxel (PTX), into the thoracic duct to examine the efficiency of drug delivery to intra-abdominal lymph nodes. We established a technical method to catheterize the thoracic duct in the necks of pigs. Serum, liver, and spleen concentrations of PTX were significantly lower after thoracic duct (IT) infusion than after intravenous (IV) administration. Approximately 12–24 h after infusion, PTX concentrations in abdominal lymph nodes tended to be higher with IT than with IV infusion; however, increased levels of PTX were much lower than expected. Unexpectedly, concentrations of PTX in urine were much higher after IT administration than after IV administration, demonstrating that most PTX administered via the thoracic duct was promptly excreted from the kidneys. These findings suggest that infusion of anti-cancer drugs into the thoracic duct will not produce clinical benefits for patients with extensive lymphatic metastases in abdominal malignancies.