Second-line treatment for malignant pleural mesothelioma

Most patients affected by malignant pleural mesothelioma (MPM) are candidates for chemotherapy during the course of the disease, as single modality treatment or within the context of a multimodality approach. Following the results of a large phase III trial, the combination of cisplatin and pemetrexed has become the preferred first-line chemotherapy, although there is also evidence for the activity of the combination with carboplatin based on phase II studies. Unfortunately, nearly all MPM patients progress during or after first-line treatment. Second-line therapies are being increasingly used in the clinical practice because patients are frequently still healthy at the time of disease progression. However, the role of these treatments in MPM is unproven, and the optimal regimens still remain to be defined. In pemetrexed-naïve patients, data from a randomized trial vs. best supportive care suggest the use of single-agent pemetrexed as a standard second-line treatment. This evidence is supported also by the results of the Expanded Access Programs. To date, there is still no standard approach for the growing population of pemetrexed-pre-treated patients. In selected cases with a prolonged response to first-line pemetrexed-based chemotherapy, re-treatment with a pemetrexed-based regimen should be considered. When a trial is not available or patients are not eligible for an experimental approach, single-agent vinorelbine can be a reasonable option for palliation. However, second-line therapy in MPM remains an ideal field in which to test new chemotherapy agents as well as new therapeutic strategies, including anti-angiogenic compounds, small molecules or monoclonal antibodies that target different molecular pathways.