Isolated lung perfusion with cisplatin in a rat lung solitary tumor nodule model.
BACKGROUND
The present study was conducted to evaluate the toxicity, pharmacokinetics and anti-tumor potency of isolated lung perfusion (ILP) with cisplatin in a visible lung tumor nodule model in rats.


METHODS
A solitary tumor nodule was established by the injection of Methylcholanthrene-induced sarcoma cells into the left lung. Thirty rats were randomized to undergo ILP with either 0.1, 0.25, or 0.5 mg/mL cisplatin and buffered hespan (BHE), or with an intravenous injection of 1.0 or 2.5 mg cisplatin.


RESULTS
The highest dose of cisplatin tolerated by the rats was 0.1 mg/mL for perfusion. A much higher platinum concentration in the tumor, of 6.67 +/- 1.64 vs. 2.51 +/- 0.60 micrograms/g tissue, but a significantly lower concentration in the serum and kidneys, was achieved by perfusion compared to that achieved by intravenous injection. A significantly lower tumor weight and 20% complete treatment response was achieved in rats given cisplatin than in those given BHE perfusion at 43.9 +/- 11.6 vs. 226.3 +/- 44.6 mg.


CONCLUSIONS
ILP with cisplatin achieved superior results to intravenous injection according to the levels of toxicity and pharmacokinetic analysis, and it was effective against a visible tumor nodule model in rats.
Li
T S
TS
First Department of Surgery, Yamaguchi University School of Medicine, Japan.
Sugi
K
K
Ueda
K
K
Nawata
K
K
Nawata
S
S
Esato
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008748:Methylcholanthrene; D011013:Pneumonectomy; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000601:surgery; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D008748:Methylcholanthrene; D002945:Cisplatin