Mesothelioma Patients - Chemotherapy
The evaluation of systemic chemotherapy in Malignant Pleural Mesothelioma (MPM) has been problematic for several reasons. Owing to the rarity of this disease, only a few randomised studies based on large numbers of participants have been implemented to provide statistically significant statements regarding response to a particular therapy.
Furthermore, inadequate imaging procedures and nonuniform staging systems have complicated data interpretation. As performed in early studies, restaging by means of chest radiography failed to determine response to a given therapy accurately. Response rates have been more reliable since CT scanning has been recognised as a diagnostic tool. In 1995, the International Mesothelioma Interest Group (IMIG) proposed a novel TNM staging system, which was designed to record data concerning the natural history of the disease and was validated in two large surgical series of mesothelioma patients (Rusch and Venkatraman, 1996; Pass et al, 1998). The universal application of this system has ever since allowed for a more prudent evaluation of results emerging from clinical studies (Pass et al, 1998; Steele and Rudd, 2000).
Early clinical trials of Malignant Pleural Mesothelioma (MPM) patients included heterogeneous groups of patients with divergent risk factors and were therefore often not powerful enough in assessing therapeutic efficacy of a particular treatment. In 1998, the European Organization for Research and Treatment of Cancer (EORTC) identified several prognostic variables for the course of the disease. In a multivariate analysis of the EORTC, poor prognosis was associated with the sarcomatous histologic subtype, male gender, poor performance status and a high white blood cell count (Curran et al, 1998). Likewise, the Cancer and Leukemia Group B (CALGB) analysed several pretreatment factors pooled from seven phase II studies that were predictive of poor survival and defined six prognostic groups. Poor prognosis was seen in patients with the following criteria: age older than 75 years, poor performance status, chest pain, dyspnoea, weight loss, high white blood cell count, elevated platelet count, low haemoglobin, elevated serum lactate dehydrogenase levels, pleural effusion and nonepithelial histology.
Owing to the establishment of prognostic scoring systems, identification of risk groups facilitated improved study design by evaluating more homogeneous patient groups or risk-group stratification in the course of randomisation (Curran et al, 1998).
The following sections summarise conventional single-agent and combination chemotherapy strategies. Results emerging from recent clinical studies with novel cytotoxic agents and their combinations are then presented, which have been published since the last review of chemotherapy in Malignant Pleural Mesothelioma (MPM).
Tables 1, 2 and 3 summarise phase II-III single-agent and combination chemotherapy trials for Malignant Pleural Mesothelioma (MPM) including more than 15 patients, which have been conducted since 1995.