Malignant pleural mesothelioma

PURPOSE The etiology, diagnosis, staging, and management of malignant pleural mesothelioma (MPM) are reviewed, with an emphasis on clinical trials of newer approaches to first-line, second-line, and adjuvant chemotherapy.

In the past decade, more effective chemotherapy regimens have been developed for patients with MPM, a rapidly progressing disease linked to a history of asbestos exposure in about 70% of cases. Patients with MPM often require multimodal treatment with surgery, radiotherapy, and adjuvant or neoadjuvant (presurgical) chemotherapy. The current standard of first-line chemotherapy for MPM is cisplatin or carboplatin in combination with pemetrexed, an antifolate compound that has been shown to increase the cytotoxic effects of platinum-based drugs. In Phase II and III clinical trials, combination therapy with pemetrexed and either cisplatin or carboplatin yielded some of the highest rates of tumor response (21-41%) and overall survival (about 12-14 months) reported to date. Dual-agent neoadjuvant chemotherapy (cisplatin plus gemcitabine or pemetrexed) followed by radical surgery with or without radiotherapy has been reported to yield median survival of up to 23-29 months in small clinical trials, but larger randomized controlled studies are needed to better define the role of neoadjuvant therapy in MPM management. Other chemotherapeutic agents that have been used against MPM, with variable results, include gemcitabine, vinorelbine, taxanes, anthracyclines, and molecular-targeted agents.

Treatment approaches for MPM include surgery, radiation, and systemic chemotherapy. MPM carries a poor prognosis, but recent studies of pemetrexed and platinum analogue combination therapies have demonstrated improved response rates over other treatments.