Isolated lung perfusion with cisplatin in a rat lung solitary tumor nodule model

Anticancer Res. 1998 Nov-Dec;18(6A):4171-6.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Body Weight / drug effects
  • Chemotherapy, Cancer, Regional Perfusion / methods*
  • Cisplatin / administration & dosage*
  • Cisplatin / pharmacokinetics
  • Cisplatin / therapeutic use
  • Cisplatin / toxicity
  • Lung / drug effects
  • Lung / pathology*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / surgery
  • Male
  • Methylcholanthrene
  • Pneumonectomy
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Rats
  • Rats, Inbred F344
  • Sarcoma, Experimental / chemically induced
  • Sarcoma, Experimental / drug therapy*
  • Sarcoma, Experimental / surgery
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Methylcholanthrene
  • Cisplatin