Treatment of Mesothelioma

 

The standard treatment for mesothelioma is often referred to as best supportive care (BSC) or active symptom control (ASC), to highlight the fact that the doctors and nurses will be seeking actively to identify and relieve symptoms of the disease. Increasingly chemotherapy is regarded as part of standard treatment for patients fit enough to receive it.

In the earlier stages of pleural mesothelioma there is often a recurrent pleural effusion which causes breathlessness. This is dealt with by pleurodesis which means inducing adhesions between the lung and chest wall. This closes off the pleural space so the effusion cannot reform. It is usually performed by putting sterile talc into the chest through the tube used to drain the fluid.

Chest pain is another common problem. Painkilling drugs are usually effective. If pain remains severe despite drugs a minor surgical procedure called cordotomy can be effective. This is done under local anaesthesia and the aim is to disable the pain carrying nerves in the spinal cord. Various other symptoms including sweating, loss of appetite and weight may also be helped by medication.

 

Surgery for Mesothelioma

 

In some cases it is helpful to remove the pleura from around the lung to help the lung to expand better, a procedure known as pleurectomy (sometimes referred to as decortication). This procedure cannot eliminate the mesothelioma completely and it grows back again.

Extended pleurectomy and decortication is a major operation involving removal of the layer of pleura lining the chest cavity, the layer of the pleura applied to the lung, and if necessary parts of the diaphragm, the muscle which separates the lung from the abdomen, and the pericardium, the membrane covering the heart. Some surgeons believe this operation prolongs survival in selected cases but this has not yet been proven. An even more radical operation known as extra-pleural pneumonectomy involves removing the entire lung as well as the pleura. This operation has fallen out of favour in the UK following a study which showed that it did not prolong average survival.

 

Radiotherapy for Mesothelioma

 

Some doctors recommend radiotherapy to the chest wall at the sites of chest drain insertion or a biopsy in order to prevent the mesothelioma growing through the skin. There is some uncertainty as to the effectiveness of this treatment and some doctors do not believe it is worthwhile.

There are two main uses of radiotherapy to treat symptoms. One is to treat a chest wall tumour which is forming a lump beneath the skin and which is causing discomfort or pain. Radiotherapy can shrink the lump and alleviate pain. The other is to relieve deeper seated pain which is not responding well to pain relieving drug therapy.

 

Chemotherapy for Mesothelioma

 

Chemotherapy can prolong survival in patients with mesothelioma. The average gain is around 2 to 3 months. This may not sound very much but the average represents some patients whose mesotheliomas do not respond to therapy who may not live any longer than they would have done without chemotherapy and others whose mesotheliomas respond well and whose survival gain is more than the average of three months. As yet there is no way to predict before treatment starts which mesotheliomas will respond well and which will not.

The chemotherapy of first choice is pemetrexed (trade name Alimta) in combination with either cisplatin or carboplatin. The drugs are given through a drip in an arm vein. The treatment is given on an out-patient basis and does not require hospitalization. Usually 4 to 6 cycles are administered at 3 week intervals.

A CT scan is performed after every 2 or 3 cycles to assess progress. If the mesothelioma has stayed the same size or shrunk treatment is continued but if the tumour has grown treatment is discontinued.  The treatment is generally well tolerated and can help symptoms of the illness as well as prolong survival. However, some patients do not tolerate it well in which case it is discontinued. Side effects are usually not severe but can include sore mouth and eyes, tiredness and sickness. There is usually little, if any, hair loss.

Another type of chemotherapy used is vinorelbine (trade name Navelbine). This can also relieve symptoms of mesothelioma and it can probably prolong life by an average of 2 months, although the evidence for prolongation of life is less strong than for pemetrexed. This drug has the advantage of being available in tablet form so the treatment can be given without the need for hospital admission. It is usually well tolerated without serious side effects. Vinorelbine can be used as second line therapy in patients who have previously received pemetrexed.

 

Mesothelioma Research

Clinical Trials

 

There is a recently opened randomised trial known as MARS-2 which aims to assess the value of major surgery called extended pleurectomy and decortication, ie stripping of the parietal pleura lining the ribcage, the visceral pleura from around the lung and resection of the diaphragm and pericardium if they are involved by tumour. Patients are randomly allocated to received standard chemotherapy alone or chemotherapy plus surgery.

A recent randomised trial showed significant prolongation of survival by a median of 2.7 months with the addition of bevacizumab to standard chemotherapy with pemetrexed and cisplatin. Bevacizumab is expensive and unlikely to be approved by NICE for the treatment of mesothelioma.

Various new biological agents are under investigation. There have been promising response rates in early trials with ADI – PEG and with Pembrolizumab. A randomised trial comparing standard chemotherapy with standard chemotherapy plus ADI – PEG known as the TRAP trial is under way.

 

Immunotherapy

 

Early-stage clinical trials have suggested benefit for mesothelioma patients from a new class of drugs known as immune checkpoint inhibitors. These drugs increase the effectiveness of the body’s natural defences against cancer. They are of proven value in treatment of some cancers, for example melanoma and non-small cell lung cancer. A small trial using one of these agents, pembrolizumab (Keytruda), in patients with pleural mesothelioma who had previously received chemotherapy, reported benefit in terms of slowing disease progression or shrinking the tumour in three quarters of patients treated (Alley et al 2016). Randomised studies of immune checkpoint inhibitors in treatment of mesothelioma are in progress to determine if benefit can be proven.

The emergence of new drugs gives real hope for improvement in the outlook in the foreseeable future.

 Clinical Trial written in search bar on virtual screen

More information on clinical trials for mesothelioma is available from the UK Clinical Trial Gateway:

https://www.ukctg.nihr.ac.uk/trials/mesothelioma

 

 

Source: Dr Robin Rudd, MA MD FRCP, Consultant Oncologist

Bart’s Mesothelioma Research

Reviewed by Dr Robin Rudd: March 2017
Due for review: March 2018

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