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Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma

2006/03/31 by William G. Richards, Lambros Zellos, Raphael Bueno +8 · 1 citation
Medicine · #Occupational and environmental lung diseases #Pleural and Pulmonary Diseases #Myasthenia Gravis and Thymoma

paper · pdf · doi:10.1200/jco.2005.04.6813

openalex publication_date 2006/03/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22

Abstract

PURPOSE: To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42 degrees C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. RESULTS: Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. CONCLUSION: Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.

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