Elsevier

Lung Cancer

Volume 55, Issue 3, March 2007, Pages 379-387
Lung Cancer

A retrospective analysis of malignant pleural mesothelioma patients treated either with chemotherapy or best supportive care between 1990 and 2005: A single institution experience

https://doi.org/10.1016/j.lungcan.2006.11.005Get rights and content

Summary

The aim of this study was to investigate the efficacy and safety profile of chemotherapy (CT) compared to best supportive care (BSC) in patients with histopathologically confirmed diffuse malignant pleural mesothelioma (DMPM). A total of 161 patients between 1990 and 2004 treated either with CT (109 patients) or BSC (52 patients) depending on patients choice were evaluated in this analyses. Chemotherapy protocols included a combination of cisplatin, mitomycin C and recombinant interferon alpha 2a (CM-In), or cisplatin, mitomycin C and ifosfamide (CMI), or cisplatin and gemcitabine (CG).

We found a significant difference in the median survivals of the patients with CT compared to BSC, 11.3 months versus 8.0. Objective response rate was 28/109 (25.7%) with 3.7% of complete response rate. Stable disease rate was 39/109 (35.8%). There was a significant difference between median survivals of patients with objective response (17 months) and median survivals of patients with progressive diseases (6 months) and also with stable diseases (16 months). There was a significant difference between the stable disease and the progressive disease. Stages 3 and 4 patients of epithelial cell type having received chemotherapy live longer than those not having received chemotherapy (12 months versus 4). There was no significant difference between the survivals of the different chemotherapy regimens. The toxicity with CT regimens were mild and well-tolerated.

We conclude that CT prolongs survival compared to BSC in patients with DMPM. Survivals of patients with objective response prolong considerably with CT compared BSC. We observed that stages 3 and 4 patients with epithelial cell type got benefit from CT. Especially, of epithelial cell type stages 1 and 2 should receive multimodal treatment.

Introduction

Diffuse malignant pleural mesothelioma (DMPM) is a highly lethal neoplasm. In most published series reported median survival for this disease is around 1- and 5-year survival rate is less than 5% [1], [2], [3], [4].

Multi-modality treatment regimens slightly prolong survival in small number of patients in whom radical surgery is possible [5], [6]. However, only 5% of the patients with DMPM are usually eligible for such a curative surgery at the time of diagnosis [7]. For this reason, most of the DMPM patients are often treated with chemotherapy (CT) or best supportive care (BSC) [8], [9], [10], [11], [12], [13], [14]. The overall response rate is around 30% and this is not very satisfactory with CT regimens. Median survival time has not been long enough to justify chemotherapy schedules until recently. Nonetheless, some studies have suggested that mesothelioma may not be totally chemotherapy-resistant and that some chemotherapeutics are moderately effective or tolerable, especially for responders [8], [9], [10], [11], [13], [14], [15]. In addition, combinations of novel chemotherapeutic agents, such as gemcitabine-cisplatin, oxaliplatin-raltitrexed, cisplatin-raltitrexed appeared to give promising results with response rates of more than 30% [16], [17], [18]. However, it was determined in these studies that median survival rates of patients receiving chemotherapy were not significantly higher than groups not receiving chemotherapy or receiving some other protocols, thus no clear indications concerning a standard treatment of DMPM had been suggested for CT regimens until the study performed by Vogelzang and colleagues [2], [4], [8], [11], [14], [15], [19], [20], [21], [22].

The efficacy of CT in mesothelioma still remains unclear. There is still a lack of solid evidence as to which stage and cell type of patients with mesothelioma could benefit from CT or BSC. Because there are pathological and clinical differences as well as clear differences in terms of prognosis between epithelial cell type and, mixed and sarcomatous cell types [4]. Although it was indicated in studies performed up to now that patients at early phase of epithelial type have benefited from multimodality treatment including surgery, there is no indication regarding whether multimodality therapy will prove beneficial for patients with mixed and sarcomatous cell types [5], [6], [22]. Some centers even consider these cell types inappropriate for surgery. Again there is no sufficient information yet concerning some other antitumoral treatment activities for this cell type. Still, it is important that new types of therapies, including CT, should be developed for mesothelioma, which is expected to claim the lives of more than 200,000 people in the coming 30 years [23].

Considering the stages and histological types, this retrospective study investigated the survival rates, responses to the treatment, side effects of the treatment of the patients receiving CT or BSC between 1990 and 2005.

Section snippets

Patient characteristics

Between January 1991 and 2005, 190 patients with histologically proven DMPM were monitored in our clinic with either CT or BSC depending on the choice of the patients. Some of these patients were at early stage and had epithelial subtype; however, they refused to undergo surgery in a multimodality schedule. Of the 190 patients, 121 were given chemotherapy, while another 69 were given only best supportive therapy. However, 161 of a total of 190 patients included in this study were sufficiently

Results

Patients (n = 29), who died within 2 months of the diagnosis, and those who abandoned the follow-up period early, and a few patients receiving different regimens and those receiving surgical operation was excluded from analysis.

The characteristics of these patients according to treatment arms were shown in Table 1.

We found a statistically significant difference between the median survivals of the patients who received chemotherapy and of those who received best supportive care alone (Fig. 1).

Discussion

Although mesothelioma is a rare disease, the incidence of DMPM is still increasing and is expected to increase due to abundant inhalation of asbestos fibers in the near past for developed countries [4], [23], [30]. This trend will probably continue in many developed countries until the second decade of the 21st century due to the long latency period (about 40 years) [31]. On the other hand asbestos exposure is still present in developing countries and legislations are not adequate to achieve

Conflict of interest

None.

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