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Isolated lung perfusion with cisplatin in a rat lung solitary tumor nodule model
1First Department of Surgery, Yamaguchi University School of Medicine, Japan.
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.
Materials And 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.
Conclusion:
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.