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J Thorac Cardiovasc Surg 2005;130:125-130
© 2005 The American Association for Thoracic Surgery

General Thoracic Surgery

Combination chemotherapy with gemcitabine with isolated lung perfusion for the treatment of pulmonary metastases

^a Department of Thoracic and Vascular Surgery, University Hospital Antwerp, Edegem, Belgium
^b Department of Medical Oncology, University Hospital Antwerp, Edegem, Belgium
^c Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands

Received for publication April 16, 2004; revisions received July 2, 2004; accepted for publication July 13, 2004.

^_* Address for reprints: Jeroen M. H. Hendriks, MD, PhD, Department of Thoracic and Vascular Surgery, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem (Antwerp), Belgium (Email: jeroen.hendriks{at}uza.be).

OBJECTIVE: Isolated lung perfusion is an experimental technique for the treatment of lung metastases. Single-agent isolated lung perfusion does not result in complete remission. We studied the in vivo and in vitro efficacy of combinations of gemcitabine, cisplatin, and melphalan.

METHODS: In vitro, using the sulforhodamine B assay, CC531s cells were incubated with cisplatin, gemcitabine, or melphalan or with a combination of these drugs. One drug was added at concentrations causing 25% growth inhibition, whereas the second drug was added at variable concentrations. In vivo, left pulmonary metastases were induced in Wag/Rij rats by means of intravenous injection of CC531s adenocarcinoma cells. At day 7, rats underwent left isolated lung perfusion with gemcitabine (n = 7), cisplatin (n = 9), melphalan (n = 7), gemcitabine-cisplatin (n = 6), melphalan-gemcitabine (n = 6), and cisplatin-melphalan (n = 7). Death by means of metastatic disease was the end point. Survival and differences in survival were assessed by using Kaplan-Meier and log-rank testing.

RESULTS: In vitro synergistic activity was observed for melphalan-gemcitabine, whereas other combinations showed additive or antagonistic activity. In vivo treated rats lived longer compared with control animals (P < .0001). In isolated lung perfusion melphalan resulted in longer survival compared with gemcitabine (P = .0016) and cisplatin (P = .046). Isolated lung perfusion with melphalan-gemcitabine resulted in 67% survival of the rats after 90 days versus 0% in other groups.

CONCLUSIONS: Isolated lung perfusion monotherapy or combination therapy with gemcitabine, cisplatin, or melphalan resulted in significantly longer survival compared with that seen in control animals. Isolated lung perfusion combination therapy with melphalan-gemcitabine resulted in the best survival either in vitro or in vivo.

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