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

Journal of Clinical Oncology, Vol 24, No 10 (April 1), 2006: pp. 1561-1567 [Link]

William G. Richards, Lambros Zellos, Raphael Bueno, Michael T. Jaklitsch, Pasi A. Jänne, Lucian R. Chirieac, Beow Y. Yeap, Rene J. Dekkers, Phillip M. Hartigan, Leah Capalbo, David J. Sugarbaker

From the Brigham and Women’s Hospital; Dana-Farber Cancer Institute; and Massachusetts General Hospital, Boston, MA

Address reprint requests to David J. Sugarbaker, MD, Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115; e-mail:


Purpose: To evaluate morbidity, mortality, maximum-tolerated dose (MTD),and outcome of intraoperative intracavitary hyperthermic cisplatinlavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM).

Patients and Methods: Sixty-one patients were prospectively registered. Forty-fourresectable patients with MPM underwent pleurectomy, followedby a 1-hour lavage of the resection cavity with dose-escalatedcisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42°Cand then intravenous sodium thiosulfate (16 g/m2 over 6 hours).Survival estimates were compared using the log-rank test andproportional hazards regression.

Results: Median age was 71 years (range, 50 to 82 years). Twenty-fourpatients had epithelial tumors, and 20 had sarcomatous or mixedhistology. Postoperative mortality was 11% (five of 44 patients).Dose-limiting renal toxicity occurred at 250 mg/m2, establishingthe MTD at 225 mg/m2. Other morbidity included atrial fibrillation(14 of 44 patients, 32%) and deep venous thrombosis (four of44 patients, 9%). Median survival time of all registered patientswas 9 months, and the median survival time of resected patientswas 13 months. Survival estimates differed significantly forresectable 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 9months, respectively; P < .0001). Low dose level (relativerisk = 3.418) and nonepithelial histology (relative risk = 2.336)were independent risk factors for poor survival. Twenty patientswith epithelial tumors who underwent high-dose cisplatin lavagehad a 26-month median survival time.

Conclusion: Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population withrestricted surgical options. An apparent dose-related survival benefit warrants further study.