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After the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

As the incidence of malignant pleural mesothelioma (MPM) is increasing in the next decades, treatment is a challenge. The past 2 years have seen a number of promising achievements in the management of patients with MPM. Treatment of a symptomatic malignant pleural effusion through indwelling pleural catheter (IPC) may allow for an individualized treatment. Advances in the systemic treatment with targeted agents will undoubtedly gain by the discovery of a driver mutation which may be selectively targeted. In the meantime, the addition of monoclonal antibodies to a standard chemotherapy backbone might result in a modest improvement in outcome in patients selected for the presence of the ligand. New techniques in radiation therapy, pleural intensity-modulated radiotherapy, helical tomography and proton-therapy are exciting advances in multimodality treatment enhancing local control and therefore improving overall survival. The role of surgery remains controversial and should be further explored. Surgical procedures consist of extrapleural pneumonectomy or lung sparing operations like debulking of the parietal and visceral pleura by (extended) pleurectomy/decortication. Where the treatment in multimodality therapy may lead to improved disease-free survival and overall survival, the type of cyto-reductive procedure should be selected on institutional and surgeon's experience. The increase in mesothelioma incidence is matched only by the increasing number of researchers and studies. It is up to the clinicians to support these efforts by stimulating their patients to participate in this clinical research.

The role of surgery in the management of malignant pleural mesothelioma remains controversial. Surgical resection consists of different procedures for diagnostic or therapeutic reasons. The latter includes either an extrapleural pleuropneumonectomy (EPP) or lung-sparing operations like debulking of the parietal and visceral pleura by pleurectomy/decortication (P/D) or extended pleurectomy/decortication, in which further debulking of the diaphragm or pericardium is included. Because of the modest outcome of surgery as single-modality therapy, combinations of chemotherapy, surgery, and radiation therapy were initiated as a new treatment strategy to improve prognosis. The observations that patients treated with P/D had an equal to better outcome than those treated with EPP, and that EPP with perioperative chemotherapy was better than EPP alone, raises the issue whether performing a P/D with perioperative chemotherapy would result in a further improvement of outcome with a lower operative mortality than with EPP and perioperative chemotherapy. This is the rationale for the next European Organisation for Research and Treatment of Cancer trial exploring the feasibility of P/D with perioperative chemotherapy.