Improved survival after introduction of chemotherapy for malignant pleural mesothelioma in Slovenia: Population-based survey of 444 patients

Abstract

Background: Malignant pleural mesothelioma is a rare tumour with increasing frequency throughout the world. Due to long latency after exposure to asbestos, restrictions in the production and use of asbestos have not yet alleviated the burden of mesothelioma. During the last decade, several trials confirmed the benefit of systemic treatment with drugs such as doublets with cisplatina and gemcitabine or pemetrexed for carefully selected patients in good performance status. The purpose of this survey was to assess the impact of systemic treatment for the whole national population of patients with mesothelioma. PATIENTS AND METHODS.: A retrospective study included all patients in Slovenia with histologically confirmed diagnosis of malignant pleural mesothelioma in the period from 1974 till 2008. Data from the Cancer Registry of Slovenia were supplemented by review of clinical records of the Institute of Oncology in Ljubljana where virtually all non-surgical treatment for mesothelioma was performed. We analysed the incidence, treatment, and survival of patients treated in the era of infrequent chemotherapy (1974-2003, the first period) and after it (2004-2008, the second period).

Results: The survey included 444 patients, of whom 325 and 119 were diagnosed in the first and second period, respectively. Joinpoint regression analysis showed that after 1995 the trend in crude incidence rates increased more rapidly; the annual change was 0.03 per 100,000 per year before 1995 and 0.06 per 100,000 per year after. There was clear male predominance (70%) throughout the period covered by the survey. The proportion of patients above 65 years of age increased from 41.8% to 54.6% for the first and second period, respectively (p = 0.02). With a total of 52 (11.7%) operated patients, surgical treatment was rare and used only for selected patients with early disease and without comorbidity, leading to their relatively long median survival of 13.6 months. Chemotherapy was applied to 56 (17.2%) and to 96 (80.7%) patients during the first and second period, respectively. While a variety of older drugs were used in the first period, the most common regimen in the second period (applied to 91 patients) was doublet of low-dose gemcitabine in prolonged infusion and cisplatin. For the whole population of patients regardless the mode of treatment, median survival was 7.4 and 12.6 months (p-value = 0.037) for the first and second period, respectively.

Conclusions: Increasing incidence, male predominance and increased proportion of older patients confirm that the burden of mesothelioma persists in spite of a 15-years old ban in the production of asbestos. Modern chemotherapy, and in particular treatment with low-dose gemcitabine in prolonged infusion and cisplatin significantly prolonged median survival of patients with malignant pleural mesothelioma in Slovenia.

Keywords: chemotherapy; gemcitabine in prolonged infusion; incidence; malignant pleural mesothelioma; survival.

FIGURE 1

The crude incidence rates of patients with malignant pleural mesothelioma with results of trend analysis, Slovenia 1974–2008.

FIGURE 2

Number of newly diagnosed malignant pleural mesothelioma cases, number of patients treated by chemotherapy and by surgery, Slovenia 1974–2008.

FIGURE 3

Overall survival of Slovenian patients with malignant pleural mesothelioma by two time periods, 1974–2003 and 2004–2008. P-value refers to log-rank test used to compare survival distributions in the two periods.

FIGURE 4

Overall survival of patients with malignant pleural mesothelioma with respect to surgery, Slovenia 1974–2008. P-value refers to log-rank test used to compare survival distributions between the two data samples.

FIGURE 5

Overall survival of patients with malignant pleural mesothelioma with respect to systemic therapy, Slovenia 1974–2008. P-value refers to log-rank test used to compare survival distributions between the two data samples.