Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma

Background. Isolated left lung perfusion with melphalan and human tumor nec rosis factor-alpha for pulmonary metastatic adenocarcinoma in the WAG/Rij r at was studied. Methods. Survival was determined for melphalan, human tumor necrosis-alpha. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatogra phy after isolated lung perfusion or intravenous injection. On day 0, rats were injected with 2.0 x 10(6) CC531S cells intravenously. On day 7, rats u nderwent sham thoracotomy, received melphalan intravenously, or underwent i solated left lung perfusion with saline, melphalan, tumor necrosis factor, and a combination of the latter two. On day 14, tumor nodules were counted. Results. For the doses of 400 mu g tumor necrosis factor, 1,000 mu g tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 mu g), survival rates after contralateral pneumonectomy were 33%, 17%, and 80 %, respectively. Survival in all other groups was 100%. Left lung melphalan level was significantly higher after isolated lung perfusion compared to i ntravenous administration. Significantly fewer left lung nodules were found for 0.5 mg isolated lung perfusion with melphalan (28 +/- 17) compared to isolated administration (200 +/- 0) (p = 0.001), and for 1.0 mg intravenous lung perfusion with melphalan (16 +/- 10) compared to controls (171 +/- 65 ) (p = 0.00047). Tumor necrosis factor showed no significant effect. Conclusions. Isolated lung perfusion with melphalan is an effective treatme nt for pulmonary metastases from adenocarcinoma in the rat. (C) 1998 by The Society of Thoracic Surgeons.