Isolated single lung perfusion with doxorubicin is effective in eradicating soft tissue sarcoma lung metastases in a rat model

Benny Weksler, J. Lenert, B. Ng, M. Burt, H. I. Pass, D. J. Mathisen

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Abstract

The only effective therapy for patients with metastatic soft tissue sarcoma in the lung is surgical resection, with a 5-year survival of approximately 25%. Because systemic chemotherapy has not significantly affected survival in these patients, we began to investigate locoregional chemotherapy. We have previously shown that isolated single lung perfusion with doxorubicin in the rat results in higher lung tissue levels and lower systemic toxicity than does high-dose intravenous therapy. In the present study, we examined the safety of isolated lung perfusion with doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were randomized into three groups (n = 5): group I had isolated left lung perfusion with doxorubicin 320 μg/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 μg/ml and group III with doxorubicin 640 μg/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10 minutes followed by perfusion of saline solution for 5 minutes. On day 21, all animals underwent right (contralateral) pneumonectomy and were observed for over 10 days. In experiment 2, two groups of F344 rats were injected intravenously with 107 viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I (n = 12) had left isolated lung perfusion with saline solution only and group II (n = 15) had isolated lung perfusion with doxorubicin 320 μg/ml. On day 21, all animals were killed, and their lungs were stained for metastases. Routine histologic sections from three animals from group II were examined. In experiment 1, 80% of the animals in group I survived contralateral pneumonectomy. There were no survivors in groups II and III. In experiment 2, three animals died after isolated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animals in both groups had massive tumor replacement of the right (untreated) lung. Group I animals had massive tumor replacement of the left (treated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung perfusion with doxorubicin 320 μg/ml is safe and effective in eradicating experimental pulmonary sarcoma metastases in this model.

Original languageEnglish (US)
Pages (from-to)50-54
Number of pages5
JournalJournal of Thoracic and Cardiovascular Surgery
Volume107
Issue number1
StatePublished - Jan 1 1994

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Sarcoma
Doxorubicin
Perfusion
Neoplasm Metastasis
Lung
Sodium Chloride
Pneumonectomy
Inbred F344 Rats
Neoplasms
Experimental Sarcomas
Animal Rights
Drug Therapy
Methylcholanthrene
Survival
Survivors

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Isolated single lung perfusion with doxorubicin is effective in eradicating soft tissue sarcoma lung metastases in a rat model. / Weksler, Benny; Lenert, J.; Ng, B.; Burt, M.; Pass, H. I.; Mathisen, D. J.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 107, No. 1, 01.01.1994, p. 50-54.

Research output: Contribution to journalArticle

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abstract = "The only effective therapy for patients with metastatic soft tissue sarcoma in the lung is surgical resection, with a 5-year survival of approximately 25{\%}. Because systemic chemotherapy has not significantly affected survival in these patients, we began to investigate locoregional chemotherapy. We have previously shown that isolated single lung perfusion with doxorubicin in the rat results in higher lung tissue levels and lower systemic toxicity than does high-dose intravenous therapy. In the present study, we examined the safety of isolated lung perfusion with doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were randomized into three groups (n = 5): group I had isolated left lung perfusion with doxorubicin 320 μg/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 μg/ml and group III with doxorubicin 640 μg/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10 minutes followed by perfusion of saline solution for 5 minutes. On day 21, all animals underwent right (contralateral) pneumonectomy and were observed for over 10 days. In experiment 2, two groups of F344 rats were injected intravenously with 107 viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I (n = 12) had left isolated lung perfusion with saline solution only and group II (n = 15) had isolated lung perfusion with doxorubicin 320 μg/ml. On day 21, all animals were killed, and their lungs were stained for metastases. Routine histologic sections from three animals from group II were examined. In experiment 1, 80{\%} of the animals in group I survived contralateral pneumonectomy. There were no survivors in groups II and III. In experiment 2, three animals died after isolated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animals in both groups had massive tumor replacement of the right (untreated) lung. Group I animals had massive tumor replacement of the left (treated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung perfusion with doxorubicin 320 μg/ml is safe and effective in eradicating experimental pulmonary sarcoma metastases in this model.",
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N2 - The only effective therapy for patients with metastatic soft tissue sarcoma in the lung is surgical resection, with a 5-year survival of approximately 25%. Because systemic chemotherapy has not significantly affected survival in these patients, we began to investigate locoregional chemotherapy. We have previously shown that isolated single lung perfusion with doxorubicin in the rat results in higher lung tissue levels and lower systemic toxicity than does high-dose intravenous therapy. In the present study, we examined the safety of isolated lung perfusion with doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were randomized into three groups (n = 5): group I had isolated left lung perfusion with doxorubicin 320 μg/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 μg/ml and group III with doxorubicin 640 μg/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10 minutes followed by perfusion of saline solution for 5 minutes. On day 21, all animals underwent right (contralateral) pneumonectomy and were observed for over 10 days. In experiment 2, two groups of F344 rats were injected intravenously with 107 viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I (n = 12) had left isolated lung perfusion with saline solution only and group II (n = 15) had isolated lung perfusion with doxorubicin 320 μg/ml. On day 21, all animals were killed, and their lungs were stained for metastases. Routine histologic sections from three animals from group II were examined. In experiment 1, 80% of the animals in group I survived contralateral pneumonectomy. There were no survivors in groups II and III. In experiment 2, three animals died after isolated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animals in both groups had massive tumor replacement of the right (untreated) lung. Group I animals had massive tumor replacement of the left (treated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung perfusion with doxorubicin 320 μg/ml is safe and effective in eradicating experimental pulmonary sarcoma metastases in this model.

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