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Ann Thorac Surg 1995;60:1394
© 1995 The Society of Thoracic Surgeons

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Invited Commentary

Invited Commentary

Department of Melanoma/Sarcoma Medical Oncology and, Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030

See also page 1390.

Sarcomas of bone and soft tissue frequently metastasize to the lungs and infrequently involve other organs. Moreover, when pulmonary metastases develop, the majority of patients ultimately succumb to their disease despite resection, because of development of more pulmonary metastases. Finding a way to eliminate pulmonary disease in patients with sarcomas would therefore significantly improve the prognosis of this group of tumors. Results of systemic chemotherapy for patients with primary soft-tissue sarcomas have been disappointing. When Dr Burt's group published their data on single-pass isolation perfusion of the lung with doxorubicin [1], I wrote an editorial using Lewis Thomas' term ``halfway technology'' [2]. That study indicated a fivefold increase in the pulmonary concentration of doxorubicin after pulmonary artery perfusion at a concentration of 72 µg/mL and a 25-fold increase in the pulmonary concentration of doxorubicin after pulmonary artery perfusion at a concentration of 255 µg/mL compared with those achieved after systemic administration at 5 mg/kg (equivalent to 75 mg/m², a standard therapeutic dose).

Wang and colleagues from the same laboratory now report a further refinement of the approach using blood flow occlusion plus doxorubicin infusion. The drug was given at a maximum dose of 0.5 mg/kg, one tenth of the systemic dose, in a volume calculated to fill the pulmonary circulation without systemic washout (0.1 mL in the rat). This resulted in a fivefold increase in pulmonary drug concentration, tolerable toxicity, and demonstrable therapeutic advantage in a metastatic sarcoma model. Potential advantages of the approach include the possibility that it could be carried out using a balloon catheter without requiring thoracotomy. Many details remain to be worked out, however, before this approach can work its way into clinical practice. How long would a patient tolerate obstruction of a major pulmonary artery? What volume of perfusate is required in man? Is a fivefold drug increase sufficient? A 25-fold increase could be obtained by isolation perfusion. Nonetheless, these exciting results suggest that a new approach to the treatment of sarcomas may not be too far in the future. This is another half step forward.

References

1. Weksler B, Ng B, Lenert JT, Burt ME. Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection. Ann Thorac Surg 1993;56:209–14.
2. Benjamin RS. Halfway technology takes another step forward. Ann Thorac Surg 1993;56:205.

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Joe B. Putnam, Jr Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Benjamin, R. S. Articles by Putnam, J. B. Search for Related Content PubMed Articles by Benjamin, R. S. Articles by Putnam, J. B., Jr Related Collections Related Article