Regional chemotherapy via pulmonary artery with blood flow occlusion in a solitary tumor nodule model.
This study is to evaluate low dose doxorubicin pulmonary artery perfusion with blood flow occlusion compared to systemic administration in a model of solitary intrapulmonary sarcoma nodule in the rat. Tumor nodule was developed via injection of methylcholanthrene-induced sarcoma into the left lung. Doxorubicin was perfused into the left pulmonary artery at a rate of 50 microliters/min for 2 min with 20 min blood flow blockage in all experiments. Pharmacokinetics, toxicity, treatment efficacy were compared between lung perfusion groups and intravenous groups. Doxorubicin levels in tumor, left lung, right lung, heart and serum were measured. Animal daily weights were recorded and a right pneumonectomy was performed following treatment to assess toxicity and tolerated perfusion dose. Tumors were weighed following treatment to evaluate treatment efficacy. Doxorubicin delivered via pulmonary artery caused a significant higher drug level in tumor tissue and perfused lung with a low drug level in heart, right lung and serum as compared to intravenous administration. Animals in perfusion groups had normal growth pattern and survived after pneumonectomy when a dose of 0.5 mg/kg doxorubicin was perfused. Tumor weight was significantly decreased after treated with 0.5 mg/kg of doxorubicin lung perfusion as compared to same dose of doxorubicin intravenous treatment. Pulmonary artery perfusion with blood flow occlusion may offer an effective lung chemotherapeutic model. 0.5 mg/kg doxorubicin for lung perfusion has acceptable local lung toxicity and no significant systemic toxicity and is pharmacokinetically and therapeutically superior to systemic administration in this solitary intrapulmonary tumor nodule model in the rat.
Wang
H Y
HY
Thoracic Oncology Laboratory, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Hochwald
S
S
Ng
B
B
Burt
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002273:Carcinogens; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene; D011651:Pulmonary Artery; D011652:Pulmonary Circulation; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003074:Solitary Pulmonary Nodule / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D008748:Methylcholanthrene; D004317:Doxorubicin