Chest
ReviewsMalignant Pleural Mesothelioma: Update, Current Management, and Newer Therapeutic Strategies
Section snippets
Epidemiology
Wagner et al4 initially reported 33 cases of mesothelioma in a South African asbestos mining community in 1960. Since then, data have been collected through various databases in the United States, Western Europe, some Eastern European countries, and the United Kingdom. Mesothelioma is usually diagnosed in the fifth to seventh decades of life, with a strong male predominance where occupational exposure to asbestos is involved.5 There are approximately 2,500 new cases of mesothelioma annually in
Pathogenesis and Biology
Exposure to asbestos, a family of naturally occurring silicate minerals, is the main risk factor for the development of MPM. The association between asbestos exposure and cancer was first established in a case-control study of lung cancer patients in 1955.8 Several varieties of asbestos fibers occur naturally; those that are narrow and needle-like (amphiboles such as crocidolite and amosite) appear to be more carcinogenic and mutagenic in animal models and tissue culture than those that are
Clinical Manifestations and Natural History
Dyspnea and nonpleuritic chest wall pains are the most common presenting complaints of patients with MPM.19 Examination may show signs of a unilateral pleural effusion with dullness to percussion and decreased air entry at one base, with a slight right-sided predominance. Patients may also be asymptomatic, with evidence of a pleural effusion noted only incidentally on physical examination or by chest radiography. A pleural mass is often present but may be obscured by pleural fluid on chest
Biopsy
Patients presenting with a clinical picture consistent with MPM require further investigation to establish a pathologic diagnosis and the stage of disease. Thoracentesis is often the initial diagnostic intervention. Cytologic diagnosis of MPM from pleural fluid is, however, unreliable since reactive mesothelial cells and cells from other malignant tumors such as sarcomas and adenocarcinomas are often very difficult to distinguish from malignant mesothelial cells.22 As a result, histologic
Palliative Care
Given that the prognosis for patients with mesothelioma has been historically poor regardless of the type of anticancer treatment, palliation of symptoms has been the primary goal of most therapy to date. Palliative therapy focuses on two major symptoms, dyspnea and chest wall pain. All previously described modalities may contribute to the palliation of patients with MPM. Radiation has shown palliative benefit in reducing pain and symptoms of dyspnea,40 surgical pleurodesis can reduce the
Novel Therapies
Several novel approaches to the treatment of MPM that incorporate new chemotherapeutic, biological, and targeted therapies are under development. Pemetrexed is a multitargeted antifolate that inhibits multiple enzymes important in folate metabolism, including thymidylate synthetase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT), and aminoimidazole carboxamide ribonucleotide formyltransferase.8182 The key enzyme targets for pemetrexed are TS, DHFR, and
Conclusion
Despite a long history of therapeutic nihilism in the treatment of MPM, recent advances have renewed enthusiasm for aggressive management of the disease in all stages. The combination of pemetrexed with cisplatin, which demonstrated a positive benefit on multiple outcomes including survival, time-to-progressive disease, and quality of life, will likely become a major component of the standard of care for patients with advanced disease, and has provided renewed hope for the development of other
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Cited by (0)
Dr. Pistolesi is a consultant of Eli Lilly and Company in the phase III study of pemetrexed in malignant pleural mesothelioma.
Dr. Rusthoven is a consultant and former employee of Eli Lilly and Company.