Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma.
BACKGROUND
Isolated left lung perfusion with melphalan and human tumor necrosis factor-alpha for pulmonary metastatic adenocarcinoma in the WAG/Rij rat was studied.


METHODS
Survival was determined for melphalan, human tumor necrosis-alpha. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatography 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 underwent sham thoracotomy, received melphalan intravenously, or underwent isolated 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 microg tumor necrosis factor, 1,000 microg tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 microg), 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 intravenous 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 treatment for pulmonary metastases from adenocarcinoma in the rat.
Hendriks
J M
JM
Laboratory for Experimental Surgery, University of Antwerp, Belgium. j.hendriks@planetinternet.be
Van Schil
P E
PE
De Boeck
G
G
Lauwers
P R
PR
Van Oosterom
A A
AA
Van Marck
E A
EA
Eyskens
E J
EJ
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011013:Pneumonectomy; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan