Salih Emri
Hacettepe University School of Medicine Department of Chest Diseases, Ankara
e-mail: se06-k@tr.net
Mesotheliomas are tumors of serosal membranes lining the pleural, pericardial, and peritoneal cavities. Malignant pleural mesothelioma (MPM) is generally caused by environmental and occupational exposure to asbestos. Erionite, a natural fibrous zeolite, which can be found in volcanic tuffs, has also been found to induce MPM. Recent studies have also shown that simian virus 40 (SV40), a DNA tumor virus that contaminated polio vaccines distributed worldwide in the late 1950's and early 1960's, may be a cofactor in the development of human mesotheliomas. MPM has become considerably more frequent in the past decades and is expected to further increase until the year 2020. Incidences amounted to 12.5 per 1 million inhabitants in UK and to 0.1 per 100.000 in Germany. The incidence of MPM is actually increasing with an estimated 2.000-3000 new cases per year in the US. In the US, it is estimated that 1495 deaths will be attributed to MPM in the year 2022. MPM continues to be a serious public health problem in rural parts of Anatolia. Approximately 16 million people live in the Central and South-eastern regions of Anatolia and thus have been environmentally exposed to asbestos and erionite fibers. The estimated incidence of MPM was 43 per 1 million inhabitants in southeast of Turkey and 996 per 100.000 inhabitants in the population exposed to erionite in erionite villages in Cappadocian region of Central Anatolia. In these villages more than 50% of deaths are caused by malignant mesothelioma.A genetic predisposition could also play a role in the development of mesothelioma in certain families in these villages. Altough much has already been known of MPM etiology, therapeutic results remain poor and cure of the disease is rare. Chemotherapy or surgery or both have not been shown to prolong survival and majority of patients are dying within 6-18 months after the diagnosis.
Irradiation for MPM assists in repelling tumor growth and temporarily relieving pain , but not attaining appreciably lengthened overall survival. Single agent or combination chemotherapy has resulted in an objective response rate between 10-33% of patients.
A number of novel cytostatic agents have been introduced into clinical oncology, and their efficacy have also been tested in MPM therapy. Initial results produced by monotherapy based on new antimetabolites, along with combinations with platin compounds proved to be encouraging. In particular, premetrexed (LY 231514, ALIMTA) achived a remarkable response rate of 45% when combined with cisplatin in a phase I study. Phase II results in vitamin supplemented patients with ALIMTA single agent showed better toxicity profile and similar efficacy. The results of phase III study of ALIMTA+cisplatin vs.cisplatin in patients with MPM will be awating this year.
Likewise, preliminary results of the raltitrexed+oxaliplatin combination have shown promising activity. Single agent gemcitabine and the drug combined with cisplatin firstly appear to decrease the symptoms asscociated with tumor load.
Other ongoing trials with newer agents are doxorubicin vs. doxorubucin+onconase, ALIMTA+ best supportive care vs. best supportive care as a second line therapy in MPM and, vinorelbine vs. MVP vs. best supportive care. Other new treatment modalities in MPM were liposomal-NDDP (intrapleural) and gene therapy.
In conclusion, by applying the new TNM staging system and distinction of prognostic groups, investigations can now more preciesly be carried out and evaluated. Large randomized phase III trials are currently underway to deliver results that will further define the potential role of new drugs in this disease.
References
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