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J Thorac Cardiovasc Surg 2009;138:405-411
© 2009 The American Association for Thoracic Surgery

General Thoracic Surgery

Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: A phase II prospective study

^a Department of Thoracic Surgery, Brigham and Women's Hospital, Boston, Mass
^b Dana Farber Cancer Institute, Boston, Mass
^c Department of Medicine, Massachusetts General Hospital, Boston, Mass

Received for publication May 15, 2008; revisions received January 9, 2009; accepted for publication February 23, 2009.

^_* Address for reprints: David J. Sugarbaker, MD, Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. (Email: dsugarbaker{at}partners.org).

Objective: We sought to prospectively determine the feasibility and safety of hyperthermic intraoperative intracavitary cisplatin perfusion immediately after extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma.

Methods: Patients with malignant pleural mesothelioma who were surgical candidates underwent extrapleural pneumonectomy followed by hyperthermic intraoperative intracavitary cisplatin perfusion, consisting of a 1-hour lavage of the chest and abdomen with cisplatin (42°C) at 225 mg/m². Pharmacologic cytoprotection consisted of intravenous sodium thiosulfate with or without amifostine. Morbidity and mortality were recorded prospectively.

Results: Ninety-six (79%) of 121 enrolled patients underwent extrapleural pneumonectomy, of whom 92 (76%) received hyperthermic intraoperative intracavitary cisplatin perfusion after extrapleural pneumonectomy. Fifty-three (58%) patients had epithelial tumors, and 39 (42%) had nonepithelial histology. Hospital mortality was 4.3%. Morbidity (grade 3 or 4, 49%) included atrial fibrillation in 22 (23.9%) patients, venous thrombosis in 12 (13%) patients, and laryngeal nerve dysfunction in 10 (11%) patients. Nine patients had renal toxicity, which was attributable to cisplatin in 8 of them. Among the 27 patients who also received amifostine (910 mg/m²), 1 patient had grade 3 renal toxicity attributable to cisplatin. Recurrence of malignant pleural mesothelioma was documented in 47 (51%) patients, with ipsilateral recurrence in 17.4% of patients. The median survival of the 121 enrolled patients was 12.8 months.

Conclusions: Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy can be performed with acceptable morbidity and mortality. The use of amifostine in addition to sodium thiosulfate might reduce cisplatin-associated renal toxicity. Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy might enhance local control in the chest.

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