Neoadjuvant Chemotherapy Followed by Extrapleural Pneumonectomy in Malignant Pleural Mesothelioma Walter Weder, Peter Kestenholz, Christian Taverna, Stefan Bodis, Didier Lardinois, Monika Jerman, and Rolf A. Stahel A B S T R A C T Purpose To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). Patients and Methods Eligible patients had MPM with clinical stage T1-3, N0-2, M0 disease considered to be completely resectable and a WHO performance status of 0 to 2. Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m 2 on day 1 and gemcitabine 1,000 mg/m 2 on days 1, 8, and 15, given every 28 days. Surgery had to consist of a complete extrapleural pneumonectomy, including resection of pericardium and diaphragm. Postoperative radiotherapy was to be considered for all patients. Results Nineteen patients with MPM were included in this pilot study. According to the European Organization for Research and Treatment of Cancer prognostic score, two patients were in the good prognosis group, and 17 patients were in the poor prognosis group. The response rate to neoadjuvant chemotherapy was 32%. The major toxicity was thrombocytopenia. Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality. Major surgical complications occurred in six patients, and all were treated successfully. Thirteen patients received postoperative radiotherapy. The median survival time was 23 months. Two patients remain alive and free of disease 41 and 38 months after initiation of therapy. Conclusion For patients with potentially operable MPM, the availability of active and well-tolerated chemotherapy regimens, the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center, and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy. J Clin Oncol 22:3451-3457. © 2004 by American Society of Clinical Oncology INTRODUCTION There is no uniformly accepted standard therapy for malignant pleural mesothelioma (MPM). The best-documented potentially curative approach to MPM has been ex- trapleural pneumonectomy, followed by chemotherapy and radiotherapy (trimodal- ity approach) in selected patients with earlier stages of disease. 1 Extrapleural pneu- monectomy involves the removal of the complete pleural envelope and all of its con- tents, including the ipsilateral lung, dia- phragm, and a portion of the pericardium. The perioperative mortality of this pro- cedure was reported to be up to 31% in an initial series 2 and 15% in the 1980s, 3 but with more experience and better pre- operative management, the perioperative mortality has decreased to 4% to 7% in re- cent series. 4-8 Extrapleural pneumonectomy followed by adjuvant combination chemo- therapy and radiotherapy (trimodality ap- proach) has been pioneered by Sugarbaker et al. 9 A recent update from this group in- cluded 183 patients who were to receive the trimodality approach. 4 The median survival time in the 176 patients alive after surgery From the Division of Thoracic Surgery, Clinic and Policlinic for Radiation Oncology, and Clinic and Policlinic for Oncology, University Hospital, Zurich, Switzerland. Submitted October 8, 2003; accepted June 1, 2004. W.W. and P.K. contributed equally to this work. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Rolf Stahel, MD, Clinic and Policlinic for Oncology, University Hospital, CH-8901 Zurich, Switzerland; e-mail: rolf.stahel@usz.ch. © 2004 by American Society of Clinical Oncology 0732-183X/04/2217-3451/$20.00 DOI: 10.1200/JCO.2004.10.071 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 22  NUMBER 17  SEPTEMBER 1 2004 3451 Downloaded from ascopubs.org by 54.242.38.15 on June 18, 2022 from 054.242.038.015 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.