Chapter 120: Systemic Chemotherapy for Mesothelioma

INTRODUCTION

Mesothelioma is a rare, aggressive malignancy arising from the mesothelial surfaces of the pleura, peritoneum, pericardium, or tunica vaginalis. Incidence of the disease peaked in the United States in the mid-1990s with approximately 2500 to 3000 new cases diagnosed annually. However, its incidence in many other parts of the world, particularly in rapidly industrializing regions without sufficient asbestos regulation, will continue to rise over the next few decades.¹ Despite attempts at aggressive multimodality therapy for seemingly localized disease, prognosis for mesothelioma continues to be dismal, with median overall survival of approximately 1 year.² Since its updated indication in 2004, pemetrexed remains the only chemotherapy specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of mesothelioma. Considering the high rates of disease recurrence or progression, the development of effective systemic treatment options for mesothelioma is sorely needed.

Unfortunately, given the rarity of this disease, enrollment in clinical trials has been difficult and many studies have been halted owing to poor accrual. Low disease incidence also limits enthusiasm for funding from pharmaceutical companies and funding agencies. As a result, there is a noticeable paucity of large, randomized trials in this disease. Much of the clinical data consists of small, single-arm, investigator-initiated studies. Comparisons of outcomes between different studies is inherently difficult and is further complicated in mesothelioma by significant variability in trial designs, staging systems used, and differences in the histologic composition in each trial. As epithelioid mesothelioma has a notably better prognosis than sarcomatoid or biphasic subtypes, differences in the histologic composition of each trial confounds useful comparisons between studies.

Another obstacle to determining treatment efficacy in mesothelioma is the challenge of consistent assessment of tumor response. The applicability of standard Response Evaluation Criteria in Solid Tumors (RECIST) criteria has been limited in mesothelioma, particularly with respect to serial assessments of the pleural rind. To address this problem, a modified RECIST criteria was developed specifically for the assessment of mesothelioma (Table 120-1).³