Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

operable disease

1st line – surgery

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ACUTE
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operable disease
1st line – 

surgery

Surgery alone (extra-pleural pneumonectomy [EPP] or pleurectomy with decortication) is rarely curative, and the effect on long-term survival remains unclear.[56]​ Surgical treatment in addition to systemic chemotherapy is independently associated with improved overall survival in patients with operable malignant pleural mesothelioma.[55]

EPP removes the parietal and visceral pleura, ipsilateral lung and pericardium, and the hemidiaphragm en bloc.

Pleurectomy with decortication is a more limited procedure involving removal of the parietal pleura from the chest wall, mediastinum, pericardium, and diaphragm, as well as removal of the visceral pleura from the ipsilateral lung (decortication). The ipsilateral lung remains intact.

The superiority of EPP over pleurectomy with decortication has not been demonstrated, but EPP does facilitate postoperative radiotherapy, which seems to decrease the risk of local recurrence.[56][57][58] However, the risk of developing a complication after EPP is high, even in experienced centres.[57] EPP is most appropriate for patients with epithelioid histology, no lymph node involvement, and sufficient cardiac and pulmonary reserve.

Plus – pre- and/or postoperative chemotherapy

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ACUTE
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operable disease
Plus – 

pre- and/or postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

In patients with potentially resectable malignant pleural mesothelioma, chemotherapy can be given preoperatively to facilitate resection and improve survival. Most studies have used cisplatin-based doublets with response rates of about 30%, with about 75% of patients subsequently undergoing extra-pleural pneumonectomy (EPP).[44][60][61][62]

Similarly, in patients who have undergone EPP, adjuvant cisplatin-based chemotherapy is often administered.

Cisplatin is associated with nephrotoxicity, nausea, and vomiting. Carboplatin may be substituted for cisplatin based on its favourable safety profile and ease of administration.[2][38] Although trials comparing cisplatin and carboplatin are not available, based on single-arm phase 2 trials, the efficacy is similar.[64]​​

Vitamin supplementation, particularly B12 and folic acid, should be added to reduce the risk of haematological toxicity associated with pemetrexed.

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

or

carboplatin

-- AND --

pemetrexed

Consider – radiotherapy

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ACUTE
|
operable disease
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Post-extrapleural pneumonectomy (EPP) radiotherapy (RT) to the ipsilateral chest cavity and chest wall can be used as adjuvant therapy, or to relieve symptoms arising from local/regional growth of tumour.[38]

RT may be used to reduce the risk of failure after EPP; some studies have shown promising rates of local control after EPP and RT using intensity-modulated techniques.[44][56]​​[73]​​​​ However, care must be taken to limit the dose to the contralateral lung, given the possibility of lethal pulmonary injury.[74]​ A trial of high-dose hemithoracic RT after neoadjuvant chemotherapy and EPP has not shown a significant improvement in locoregional relapse-free survival in patients who received postoperative RT.[75]​ However, this study was methodologically flawed.

Comprehensive RT after pleurectomy with decortication is not recommended due to the risk of radiation pneumonitis.[38]​ Even with moderate postoperative doses of RT the risk of local failure remains high and, because the ipsilateral lung remains intact, the risk of radiation pneumonitis is prohibitive.[76][77] Improved radiation delivery techniques, such as intensity-modulated radiotherapy (IMRT) may allow delivery of adequate doses to target structures while minimising the risk of radiation pneumonitis.[78][79]

inoperable or recurrent disease

1st line – chemotherapy and/or immunotherapy

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ACUTE
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inoperable or recurrent disease
1st line – 

chemotherapy and/or immunotherapy

In patients with inoperable or recurrent mesothelioma, chemotherapy and/or immunotherapy is often given in an attempt to improve quality of life and survival.

Specifically, patients with inoperable malignant disease should receive combination chemotherapy (pemetrexed plus cisplatin or carboplatin with or without bevacizumab) or combination immune checkpoint inhibitor therapy (nivolumab plus ipilimumab).[2]

Generally, it is appropriate to treat patients with an alternative first-line regimen if another has failed: for example, trial immune checkpoint inhibitor therapy if first-line chemotherapy has failed (and vice versa).[2]

Nivolumab alone, pemetrexed alone, vinorelbine alone, or gemcitabine with or without ramucirumab may be offered as second-line therapies.[2][38][72]​​

Vitamin supplementation, particularly B12 and folic acid, should be added to reduce the risk of haematological toxicity associated with pemetrexed.

Cisplatin is associated with nephrotoxicity, nausea, and vomiting. Carboplatin may be substituted for cisplatin based on its favourable safety profile and ease of administration.[2][38] Although trials comparing cisplatin and carboplatin are not available, the efficacy is similar in single-arm phase 2 trials.[64]​​

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

or

carboplatin

-- AND --

pemetrexed

OR

cisplatin

or

carboplatin

-- AND --

pemetrexed

-- AND --

bevacizumab

OR

nivolumab

and

ipilimumab

Secondary options

nivolumab

OR

pemetrexed

OR

vinorelbine

OR

gemcitabine

OR

gemcitabine

and

ramucirumab

Consider – radiotherapy

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ACUTE
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inoperable or recurrent disease
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy can be used to palliate local sites of disease that may be causing distressing symptoms, most commonly pain due to chest wall invasion or shortness of breath due to airway obstruction.

Consider – palliative procedures + supportive care

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ACUTE
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inoperable or recurrent disease
Consider – 

palliative procedures + supportive care

Additional treatment recommended for SOME patients in selected patient group

Therapeutic thoracentesis and pleurodesis may provide symptomatic relief.

In addition to aiding diagnosis, thoracentesis can often provide temporary relief for those patients suffering from dyspnoea as a consequence of a large pleural effusion. In patients with breathlessness, aggressive daily drainage provides no additional benefit over a symptom-driven approach.[85]

Pleurodesis, defined as the artificial obliteration of the pleural space, can be performed to prevent re-accumulation of pleuritic fluid. Talc pleurodesis seems to be the most effective sclerosant.[86] [ Cochrane Clinical Answers logo ] ​Video-assisted thoracoscopic surgery (VATS) pleurodesis provides optimal results.[86] One randomised study showed that VATS partial pleurectomy was not superior to talc pleurodesis in terms of improving survival or symptom control.[87]

Certain interventions may help to improve symptoms, psychological functioning, and quality of life.[88]​ Some examples include nursing programmes, interventions to manage breathlessness, and counselling, as well as psychotherapeutic, psychosocial, and educational interventions.[88]

Early referral to specialist palliative care (SPC) does not improve health-related quality of life in patients who are cared for in centres with good access to SPC when required.[90]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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