Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.

J Thorac Cardiovasc 1999 Apr;117(4):759-65
Ratto GB, Civalleri D, Esposito M, Spessa E, Alloisio A, De Cian F, Vannozzi MO
Istituto Anatomia Chirugica and Istituto Clinica Chirurgica, University of Genoa, Istituto Nazionale per la Ricerca sul Cancro, Servizio di Farmacologica Tossicologica, Genoa, Italy.

INTRODUCTION: Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior.

METHODS: This mesothelioma study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41.5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia.

RESULTS: The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platimum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were reached after pleurectomy/decortication that after pleuropneumonectomy (P=.006). The local tissue/perfusate ratio of platimum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion.

CONCLUSION: This multimodality appraoch is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.

Source

PMID: 9689814, UI: 98354239
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Raphael Bueno, M.D.
Dr. Raphael Bueno is the Associate Chief of Medicine in the Division of Thoracic Surgery at Boston's Brigham and Women's Hospital specializing in the treatment of malignant mesothelioma.

Thierry Marie Jahan, M.D.
Dr. Thierry Marie Jahan is the Associate Clinical Professor of Medicine at the University of California San Francisco and is dedicated to the treatment of mesothelioma.

David Rice, M.D.
Dr. David Rice is an Associate Professor and Assistant Surgeon at The University of Texas M.D. Anderson Cancer Center where he serves as the director of the Minimally Invasive Surgery and Mesothelioma programs.

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