Systemic Treatment of Malignant Pleural Mesothelioma

Federica Grosso; Giorgio Vittorio Scagliotti

Disclosures

Future Oncol. 2012;8(3):293-305. 

In This Article

Abstract and Introduction

Abstract

Malignant pleural mesothelioma is a rare malignancy with a dismal prognosis. The clinical management of most of the patients with this disease is quite challenging, and, overall, the therapeutic strategy has not yet benefited from the recent advances in molecular biology. Randomized evidence supports the use of cisplatin in combination with pemetrexed or raltitrexed as first-line treatments. In elderly patients with comorbidities cisplatin may be replaced by carboplatin because of a lesser burden of toxicities. The role of second-line chemotherapy is unproven, although pemetrexed can be regarded as the standard option in pemetrexed-naive patients and therapeutic rechallenge with pemetrexed may be considered in selected patients with prolonged disease control after first-line therapy. Targeted therapies failed to demonstrate any substantial activity; however, immunotherapies may complement other treatment strategies. In summary, there is an unmet clinical need and innovative approaches to select new potentially active drugs are highly warranted.

Introduction

Malignant pleural mesothelioma (MPM) accounts for approximately 80% of all mesotheliomas.[1] A direct causal relationship with asbestos exposure was described for the first time in 1960;[2] approximately 80% of male patients had an occupational exposure.[3] The incidence is approximately 2/100,000 cases each year in Europe and approximately 1.1/100,000 cases each year in the USA.[4,201] While in most European countries the incidence is anticipated to increase in the next 10 years, in the USA it seems to have peaked between 2000 and 2005 and is now decreasing in line with the decline in asbestos exposure, and this trend is expected to continue.[5,6] On the contrary, the global incidence continues to rise since some countries, such as Russia, China, Kazakhstan, Brazil and Canada, still extract and manufacture large amounts of asbestos and it is also still employed in other developing countries such as India.[7]

MPM patients have a very dismal prognosis with median overall survival (OS) ranging from 4 to 13 months for untreated patients and from 6 to 18 months for treated patients.[8,9] The prognosis is worse in male patients, in those with advanced-stage disease, poor performance status, elevated white blood cell counts, anemia, thrombocytosis and sarcomatoid histology, regardless of the therapeutic approach.[10]

Radical surgery with extrapleural pneumonectomy within a trimodal strategy, including neoadjuvant chemotherapy and adjuvant hemithoracic radiotherapy, has been associated with encouraging long-term disease control, mainly in Phase II studies. However, the benefit of this approach, if any, is confined to a subset of selected patients; that is, those with good performance status, epithelioid histology or earlier disease stage (T1–T2, N0–N1 and M0).[11–15] By contrast, a recently published randomized study on extrapleural pneumonectomy within trimodal strategies failed to demonstrate any benefit and seemed to be harmful for patients.[16] This at least questions the role of surgery with curative intent in this disease. Pleurectomy/decortication can achieve macroscopic complete resection only in patients with very limited disease, and in a large, retrospective study, it has been suggested to provide a survival advantage compared with extrapleural pneumonectomy. Its impact on delaying tumor progression and prolonging survival is still controversial, and pleurectomy/decortication is generally used to provide palliation in case of entrapped lung, and can be of benefit especially when performed by video-assisted thoracoscopic surgery.[17,18]

Systemic therapy represents the mainstay of treatment for the majority of MPM patients. Nevertheless, talc pleurodesis is still the only treatment that many institutions offer, even to patients fit for systemic approaches. This review is aimed at updating on current systemic management of MPM, focusing on chemotherapy and novel biological therapies.

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