Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Abstract

This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II -III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine -applied as a single agent or in combination with cisplatin -as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.

Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed

“…Gemcitabine and pemetrexed have already been shown to be particularly effective in combination with cisplatin for MMe chemotherapy. 29 We therefore tested the cytotoxic effect induced by these two agents in the presence of different concentrations of imatinib. As expected, gemcitabine and pemetrexed killed MMe cells in a dose-dependent manner.…”

“…Combined treatment with cisplatin/pemetrexed and cisplatin/gemcitabine have been found to be more effective than each single agent used alone. 29 The aim of the present study is to investigate a translational approach which assesses the possible efficacy of imatinib as a single agent and in combination treatment for MMe.…”

FLIP overexpression inhibits death receptor-induced apoptosis in malignant mesothelial cells

“…Mesothelioma is a chemoresistant malignancy. Only multimodality regimens of treatment, based on surgery, radiotherapy and chemotherapy, improve the long-term survival for a very small subgroup of patients (Jaklitsch et al, 2001;Tomek et al, 2003). Furthermore, it has been shown that MM patients have impaired immune responsiveness (Manning et al, 1991).…”

Induction of Stem Cell Factor/c-Kit/Slug Signal Transduction in Multidrug-resistant Malignant Mesothelioma Cells

“…MM cells exhibit resistance in vitro and in vivo to many anti-cancer agents, including doxorubicin and cisplatin, which are nevertheless widely used to treat MM (4). In most cases, this is the consequence of overexpression of the ATP-binding cassette (ABC) transporters, including MDR1 (ABCB1), MRP1 (ABCC1), and MRP2 (5).…”