Chemotherapy for malignant mesothelioma

Abstract

0 d er to identify single drugs or combinations that how any activity in malignant pleural mesotheioma (MPM). In general, the reported level of acivity of these drugs was low, for which different easons could be given. Many of the phase II studies ave been poorly designed with too few patients nd many studies did not have standard review of he pathology specimen to rule out patients with ther types of cancer. Furthermore, mixtures of the ifferent types of mesotheliomas within studies ocurred, which also lead to a statistical bias of the esults. Response measurements in MPM are conidered difficult because the tumor grows along the horacic wall and significant amounts of connective issue limits the measurement of response with cerainty. CT scanning is used as follow-up but a reponse of a pleural thickness of ≤1 cm is difficult to stablish and also the usefulness of the RESIST crieria has been challenged. The presence of pleural uid makes the analysis difficult especially when it ecomes organized. A new development is the use of resection and intra-operative chemotherapy has attracted much attention. After aggressive tumor resection a lavage with chemotherapeutic drugs under hyperthermic conditions can be performed in order to kill the remaining microscopic tumor cells [1,2]. Details of this approach however will be discussed elsewhere. For many years, chemotherapy using single agents has been tested to select promising drugs and to evaluate their toxicity. Some studies with single agents have reported overall response rates in the range of 10—20% and were the basis for combination therapies. The anthracyclines (doxorubicin, epirubicin), the antifolates (high-dose methotrexate, MTX) and cisplatin are examples of such agents. In Table 1, the response rates and median survival times achieved with single agent chemotherapy are presented. A large variation in overall response rate between different researchers using the same drug is probably due to the relative small number of patients and the variation f FDG PET scanning but this approach has not yet een fully validated. Chemotherapy can be administered systemically in patient selection criteria. Therefore, the number of patients treated with comparable schedules has been pooled.