Chemotherapy and Radiotherapy for Mesothelioma

Chemotherapy
Until recently, all reviews of chemotherapy for malignant mesothelioma reported poor response rates
(typically less than 15 to 20 percent) and, because of these low rates, did not recommend a standard of
care.81 However, a number of multicenter studies are now under way, and several new therapeutic regimens
appear to be useful. Pemetrexed is a potent inhibitor of a number of proteins, including thymidylate synthase and dihydrofolate reductase, both of which are required for DNA synthesis. In a multicenter phase 3 study involving 448 patients, those treated with pemetrexed plus cisplatin had a longer overall median survival
(12.1 months) than those treated with cisplatin alone (9.3 months) and had an objective response
rate (shrinkage of the tumor by at least 50 percent) of 41 percent.82 Treatment with gemcitabine, a “false nucleotide” that is incorporated into DNA, plus cisplatin resulted in objective response rates of 48 percent and  percent in two studies, as well as symptomatic improvement and quality-of-life benefits.83 Imatinib
(Gleevec) and gefitinib (Iressa) block the platelet- derived growth factor and epidermal growth factor
signaling pathways, respectively. Both of these pathways are active in malignant mesothelioma.
Early studies of the treatment of mesothelioma with these compounds, however, have yielded no convincing
evidence of a response.
Radiotherapy:
Malignant mesothelioma is resistant to traditional radiotherapy.85 Local radiotherapy directed to surgical
sites prevents seeding of tumor, and radiotherapy can provide palliative relief of somatic chest-wall pain.85 The diffuse nature of the tumor, which often covers most of the lung and the interlobular fissures,
is the principal limitation to radiotherapy. However, even when the affected lung is removed,
radiotherapy is of limited effectiveness.86 The most successful fractionation method is intensity- modulated radiotherapy,86 a technique generally used after radical surgical resection of malignant mesothelioma. This approach controls local recurrence, but many patients die of metastatic disease.
 The use of radioactive colloids and other forms of brachytherapy in the pleural or peritoneal
cavity is logical, but the results have been disappointing.

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