Isolated lung perfusion with melphalan for the treatment of metastatic pulmonary sarcoma Journal Article


Authors: Nawata, S.; Abecasis, N.; Ross, H. M.; Abolhoda, A.; Cheng, H.; Sachar, K. S.; Burt, M. E.
Article Title: Isolated lung perfusion with melphalan for the treatment of metastatic pulmonary sarcoma
Abstract: Objective: Isolated lung perfusion allows the delivery of high-dose chemotherapy to the perfused lung and is an efficacious modality in the treatment of pulmonary metastases in the rat. Melphalan activity in this model was investigated. Methods: TOXICITY STUDY: Maximum tolerated dose of melphalan delivered by means of isolated lung perfusion was determined by survival after contralateral pneumonectomy. PHARMACOKINETICS STUDY: Nineteen rats were treated with melphalan administered either by isolated lung perfusion (2 mg) or intravenously (2 mg or 1 mg). Lung, pulmonary effluent, and serum melphalan were analyzed by high-pressure liquid chromatography. EFFICACY STUDY: On day 0, 41 rats received an intravenous injection of 5 x 106 methylcholanthrene induced sarcoma cells. On day 7, rats either received intravenous melphalan (2 mg [n = 10]; 1 mg [n = 81) or underwent left isolated lung perfusion with 2 mg of melphalan (n = 12). Isolated lung perfusion with buffered hetastarch in sodium chloride (Hespan, n = 11) was used as control. On day 14, pulmonary nodules were counted. Results: TOXICITY: Maximum tolerated dose of melphalan delivered buy means of isolated lung perfusion was 2 mg. PHARMACOKINETICS: Left lung melphalan level was significantly higher in the isolated lung perfusion group (62.2 ± 34.3 μg/gm lung) than in the intravenous treatment groups (6.9 ± 1.9 μg/gm lung and 3.3 ± 0.9 μg/gm lung, respectively) (p = 0.0002). EFFICACY: Significantly fewer left lung nodules were found in animals receiving melphalan by means of isolated lung perfusion (7 ± 10) than in the groups receiving intravenous melphalan (60 ± 21) or buffered hetastarch by isolated lung perfusion (84 ± 52) (p = 0.01 and p = 0.0001, respectively). Conclusion: Isolated lung perfusion with melphalan is safe and effective in the treatment of pulmonary sarcoma metastases in the rat.
Keywords: cancer survival; controlled study; dose response; drug efficacy; nonhuman; lung resection; animal experiment; animal model; melphalan; lung metastasis; rat; regional perfusion; hetastarch; drug blood level; high performance liquid chromatography; intravenous drug administration; lung nodule; lung sarcoma; isolated lung; male; priority journal; article; lung perfusion
Journal Title: Journal of Thoracic and Cardiovascular Surgery
Volume: 112
Issue: 6
ISSN: 0022-5223
Publisher: Mosby Elsevier  
Date Published: 1996-12-01
Start Page: 1542
End Page: 1548
Language: English
DOI: 10.1016/s0022-5223(96)70013-2
PUBMED: 8975846
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Huiming   Cheng
    5 Cheng
  2. Michael E. Burt
    187 Burt
  3. Howard M. Ross
    13 Ross