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J Thorac Oncol. 2007 Mar;2(3):237-42.

Four-modality therapy in malignant pleural mesothelioma: a phase II study.

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Division of Thoracic Surgery, Cardiac and Thoracic Department, University of Pisa, Italy.



Treatment approaches in malignant pleural mesothelioma (MPM) patients range from mere palliation to aggressive anticancer therapy, and there is currently no consensus on the optimal therapeutic strategy. In 1999, we began a phase II study to investigate four-modality treatment of advanced stage MPM.


From 1999 to 2004, 49 patients with International Mesothelioma Interest Group stage II-III MPM underwent four-modality treatment with intrapleural preoperative interleukin-2 (18 x 10(6) UI/day for 3 days), pleurectomy/decortication, intrapleural postoperative epidoxorubicin (25 mg/m2 for 3 days), interleukin-2 (18 x 10(6) UI/day for 3 days), adjuvant radiotherapy (30 Gy), systemic chemotherapy (cisplatin 80 mg/m2 day 1, gemcitabine 1250 mg/m2 days 1 and 8 for up to six courses) and long-term subcutaneous interleukin-2 (3 x 10(6) UI/day on 3 days per week).


Patients included 41 men and eight women with a median age of 61 years (range, 41-77). All patients were diagnosed with MPM by thoracoscopy before inclusion. There was no postoperative mortality. Postoperative morbidity included bleeding (n = 1) and arrhythmias (n = 3). After a median follow-up of 59 months (range, 14-81), 13 patients are still alive and the median actuarial survival is 26 months (31 and 21 months for stages II and III, respectively). The 2- and 5-year actuarial survival rates were 60.2% and 23.3%, respectively. Baseline Eastern Cooperative Oncology Group performance status significantly influenced survival time (p = 0.02).


The four-modality treatment that we adopted for advanced-stage MPM was feasible, well tolerated by most of the patients, and produced a favorable median survival. This treatment approach warrants further investigation.

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