ISOLATED LUNG PERFUSION WITH FUDR IS AN EFFECTIVE TREATMENT FOR COLORECTAL ADENOCARCINOMA LUNG METASTASES IN RATS

Currently, the only treatment capable of significantly prolonging surv ival in patients with isolated pulmonary metastases from colorectal ad enocarcinoma is complete resection. Systemic chemotherapy has been sho wn to provide little benefit. We evaluated the efficacy of high-dose, organ-specific 2'-deoxy-5-fluorouridine (FUDR) using a model of isolat ed single-lung perfusion (ILP) in the rat. On day 0, 28 BDIX rats were inoculated intravenously with 10(6) viable Sp-5 colorectal adenocarci noma 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 os motic 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, resp ectively. Animals undergoing ILP were anesthetized with pentobarbital, intubated, and ventilated, and then underwent left thoracotomy with c annulation 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 buffer ed Hespan solution. On day 26 after tumor inoculation, the animals in all groups were sacrificed and their lungs were stained and counted. A nimals that underwent ILP with 14 mg of FUDR per milliliter of the buf fered Hespan solution showed a significant decrease in the number of t umor nodules on the treated side versus the number on the untreated si de (455.2 +/- 87.3 versus 11 +/- 6.4; p < 0.0001). Although the intrav enous FUDR-treated animals exhibited a decreased number of pulmonary n odules compared with the number in controls, the number of left lung p ulmonary nodules was significantly greater than that in the ILP treate d animals (216 +/- 93 versus 11 +/- 6; p < 0.05). We conclude that iso lated lung perfusion with high-dose FUDR is effective in the treatment of colorectal adenocarcinoma pulmonary metastases resistant to intrav enous therapy in a rat model.