Synergistic antitumour effect of recombinant human tumour necrosis factor a with melphalan in isolated limb perfusion in the rat

Author:

Manusama E R1,Nooijen P T G A2,Stavast J1,Durante N M C1,Marquet R L1,Eggermont A M M1

Affiliation:

1. Department of Surgery, University Hospital Rotterdam, Dr Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands

2. Department of Pathology, University of Nijmegen, The Netherlands

Abstract

Abstract The efficacy of isolated limb perfusion (ILP) for ‘intransit’ metastases from malignant melanoma and irresectable soft tissue sarcoma has been improved considerably by the addition of tumour necrosis factor (TNF) α. A rat sarcoma tumour model was, therefore, developed to evaluate the effects of TNF-α, melphalan and the combination of these drugs in the treatment of sarcoma. In BN rats bearing the non-immunogenic BN 175 sarcoma ILPs were performed with perfusate only, TNF-α, melphalan alone, or in combination when tumours had grown to approximately 1·5 cm in diameter. All rats treated with sham perfusion or perfusion with 50 μg TNF-α showed progressive disease. After perfusion with 40 μg melphalan no change in tumour diameter was observed in any rats at 4 days. After a combined perfusion with 40 μg melphalan and 50 μg TNF-α complete remission was noted in 12 of 16 rats. This synergistic effect in vivo between relatively ineffective doses of TNF-α and melphalan was not observed in vitro.

Publisher

Oxford University Press (OUP)

Subject

Surgery

Reference34 articles.

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2. Isolated perfusion of the limb with high-dose tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and melphalan for melanoma stage III. Results of a multi-centre pilot study;Lienard;Melanoma Res,1994

3. Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit;Creech;Ann Surg,1958

4. Chemotherapy of sarcomas of the limbs by regional perfusion;Krementz;Ann Surg,1977

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