Isolated lung perfusion with FUDR is an effective treatment for colorectal adenocarcinoma lung metastases in rats

Currently, the only treatment capable of significantly prolonging survival in patients with isolated pulmonary metastases from colorectal adenocarcinoma is complete resection. Systemic chemotherapy has been shown to provide little benefit. We evaluated the efficacy of highdose, organ-specific 2′-deoxy-5-fluorouridine (FUDR) using a model of isolated single-lung perfusion (ILP) in the rat. On day 0, 28 BDIX rats were inoculated intravenously with 106 viable Sp-5 colorectal adenocarcinoma cells. On day 10 after-tumor inoculation, animals were randomized into five treatment groups. Group I received a continuous intravenous infusion of FUDR (1 mg ⋅ kg−1 ⋅ d−1) for 7 days administered by an osmotic minipump. Group II underwent isolated left lung perfusion with a buffered Hespan solution, groups III to V underwent ILP with 3.5, 7, and 14 mg of FUDR per milliliter of the buffered Hespan solution, respectively. Animals undergoing ILP were anesthetized with pentobarbital, intubated, and ventilated, and then underwent left thoracotomy with cannulation of the pulmonary artery; the pulmonary artery and vein were clamped proximally. Groups II to V were perfused for 20 minutes at a rate of 1 mL/min, followed by a 5-minute washout with FUDR-free buffered Hespan solution. On day 26 after tumor inoculation, the animals in all groups were sacrificed and their lungs were stained and counted. Animals that underwent ILP with 14 mg of FUDR per milliliter of the buffered Hespan solution showed a significant decrease in the number of tumor nodules on the treated side versus the number on the untreated side (455.2 ± 87.3 versus 11 ± 6.4; p < 0.0001). Although the intravenous FUDR-treated animals exhibited a decreased number of pulmonary nodules compared with the number in controls, the number of left lung pulmonary nodules was significantly greater than that in the ILP treated animals (216 ± 93 versus 11 ± 6; p < 0.05). We conclude that isolated lung perfusion with high-dose FUDR is effective in the treatment of colorectal adenocarcinoma pulmonary metastases resistant to intravenous therapy in a rat model.