Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of pulmonary metastases.
BACKGROUND
We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin.


METHODS
In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls.


RESULTS
Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks.


CONCLUSIONS
Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.
Abolhoda
A
A
Thoracic Oncology Laboratory/Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Brooks
A
A
Nawata
S
S
Kaneda
Y
Y
Cheng
H
H
Burt
M E
ME
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D008168:Lung; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000556:secondary*; D016019:Survival Analysis
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin