Pemetrexed for the treatment of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a type of cancer that occurs in the pleura – the mesothelium (membranous lining) surrounding the lungs. MPM is a rapidly progressive malignancy of insidious onset.

Approximately 90% of cases of MPM are linked to asbestos exposure. When asbestos fibres are inhaled or swallowed, they can cause scarring of the lung tissues, cancer of the bronchial tree (lung cancer) and sometimes cancers in the pleura and peritoneum. A wide range of occupations, notably shipbuilding, railway engineering and asbestos product manufacture, are associated with an increased risk of MPM. Family members of people whose work clothes were contaminated with asbestos fibres have also developed MPM. The condition is significantly more common in men, with a male to female ratio of 5:1. People with mesothelioma usually present with the disease between the ages of 60 and 79 years.

MPM usually develops 20–50 years after exposure to asbestos. Data from 2004 suggest that about 1700 people in the UK are diagnosed with MPM each year. It is estimated that this figure will increase to a peak of more than 2000 cases each year between 2011 and 2015, reflecting a lag from the highest use of asbestos in the 1970s. An estimated 65,000 cases are expected to occur between 2002 and 2050. The use of asbestos was banned in the UK in 1999.

Most people with MPM present with chest pain and dyspnoea and have pleural effusions evident on examination. Fatigue, profuse sweating, weight loss, anorexia and difficulty in swallowing become common as the disease progresses. Presentation and diagnosis often occur at an advanced stage and the prognosis for most patients is extremely poor. Median survival from diagnosis varies in studies, with a range of 9–13 months. Age, tumour histology, tumour stage at diagnosis and performance status have been shown to be independent prognostic factors. The most commonly used performance status scoring systems include the Karnofsky performance status (KPS) and the World Health Organization (WHO) scales. KPS is a 10-point scale ranging from 0 to 100, with higher scores representing normal day-to-day activity. The WHO system is a five-point scale with lower scores representing normal day-to-day activity. In general, WHO scores of 0 and 1 are considered equivalent to KPS scores of 70–100.

There is no standard treatment pathway for MPM in England and Wales. The clinical management is multimodal and a patient may receive a combination of treatments. Staging provides prognostic information and can help to determine an appropriate treatment strategy; however, it is complex, and surgical intervention is required to stage the disease fully. There is no universally accepted staging system, but the traditional Butchart system is gradually being replaced with a tumour nodes metastases (TNM) system developed by the International Mesothelioma Interest Group. In clinical practice, MPM is generally staged pragmatically based on whether or not surgical resection is considered an appropriate option. Extrapleural pneumonectomy is an option for the small proportion of patients (1–5%) whose tumours are at stage 1 or 2.

Surgery is not indicated for the majority of patients, so treatment aims to improve symptoms and maintain quality of life for as long as possible. Often, this does not involve treating the tumour with chemotherapy. Treatment that does not include a specific anti-cancer therapy is referred to as active symptom control (ASC) or best supportive care (BSC). For people with MPM, this may include interventions to manage pain and dyspnoea, and to address psychosocial problems. Treatments may include draining excess fluid from the pleural cavity and applying a talc pleurodesis (the insertion of talc to prevent further fluid accumulation), palliative radiotherapy, analgesics, steroids, appetite stimulants and bronchodilators.

There is no standard chemotherapy treatment for MPM. Pemetrexed in combination with cisplatin is the only chemotherapy regimen that is currently licensed for this indication. However, a variety of combination and single-agent regimens such as the mitomycin C, vinblastine and cisplatin combination (MVP) or vinorelbine are used. To date there have been no published randomised controlled trials (RCTs) comparing survival and symptom control in patients receiving chemotherapy with those receiving ASC.