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J Thorac Cardiovasc Surg 2009;137:453-458
© 2009 The American Association for Thoracic Surgery

General Thoracic Surgery

A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma

^a Division of Thoracic Surgery and Department of Pathology, Brigham and Women's Hospital, Boston, Mass
^b Department of Medicine, Brigham and Women's Hospital, Boston, Mass
^c Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Mass

Received for publication January 25, 2008; revisions received June 6, 2008; accepted for publication July 17, 2008.

^_* Address for reprints: Lambros Zellos, MD, MPH, 75 Francis St, Boston MA 02115. (Email: lzellos{at}partners.org).

Objective: This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma.

Methods: Patients with mesothelioma were prospectively enrolled. Those with resectable disease received amifostine and 1-hour hyperthermic cisplatin perfusion of ipsilateral hemithorax and abdomen. Morbidity, recurrence, and survival were recorded.

Results: Forty-two patients were enrolled; 29 underwent resection (operative mortality 7%, 2/29). Median age was 57 years. Eighteen were in pathologic stage I or II; 11 were in stage III. Median hospitalization was 15 days. Common complications were atrial fibrillation (66%, 19 patients), deep venous thrombosis (31%, 9 patients), and grade 3+ renal toxicity (31%, 9 patients). Feasibility was determined. Renal toxicity was unrelated to cisplatin dose, with no maximum tolerated dose determined. Overall median survival was 17 months (resected 20 months, unresected 10 months). Median survivals were 26 months for patients receiving higher cisplatin doses and 16 months for those receiving lower doses (P = .35). Survival was significantly longer with negative extrapleural nodes (31 vs 14 months, P = .0115) and early stage (all resected 35 months for stage I–II vs 14 months for stage III, P = .0022, epithelial 39 months for stage I–II vs 15 months for stage III, P = .0072).

Conclusion: Early stage and negative extrapleural lymph nodes were associated with prolonged survival. Single-dose amifostine did not protect adequately against cisplatin-induced renal toxicity. Additional cytoprotective strategies are needed to allow determination of cisplatin maximum tolerated dose.

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				T. R. Tilleman, W. G. Richards, L. Zellos, B. E. Johnson, M. T. Jaklitsch, J. Mueller, B. Y. Yeap, A. A. Mujoomdar, C. T. Ducko, R. Bueno, et al. Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study. J. Thorac. Cardiovasc. Surg., August 1, 2009; 138(2): 405 - 411. [Abstract] [Full Text] [PDF]