Malignant Pleural Mesothelioma Treatment Protocols 

Updated: Nov 23, 2015
  • Author: Winston W Tan, MD, FACP; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment Protocols

Treatment protocols for malignant pleural mesothelioma are provided below, including general approaches and treatment by surgical intervention, chemotherapy, radiotherapy, and trimodality therapy.

General treatment approach

Stage I resectable:

  • Patients with operable disease may receive extrapleural pneumonectomy (EPP); if positive margins, add radiation therapy

Stage I unresectable:

  • Observation for disease progression or
  • Chemotherapy
  • Radiation for positive margins

Stages II-III resectable:

  • Induction chemotherapy (cisplatin and pemetrexed) or
  • Surgery (pleurectomy/decortication or extrapleural pneumonectomy)
  • Radiation

Stages II-III unresectable:

  • Chemotherapy is recommended
  • Radiation for palliation and positive margins

Stage IV:

  • Chemotherapy
  • Radiation post chemotherapy for palliation
  • Surgery is not recommended for patients with stage IV disease

Surgical resection

The 2 surgical procedures commonly used in malignant mesothelioma are pleurectomy with decortication and EPP. For patients with early stage disease with favorable histology and good-risk patients, pleurectomy/decortication (P/D) is a good option. Patients with advanced disease and mixed histology and/or high risk should undergo P/D. [1, 2]

  • Pleurectomy with decortication is a more limited procedure and requires less cardiorespiratory reserve; it involves dissection of the parietal pleura, incision of the parietal pleura, and decortication of the visceral pleura, followed by reconstruction; this procedure has a morbidity of 25% and a mortality of 2%
  • Extrapleural pneumonectomy is a more extensive procedure than pleurectomy with decortication and has a higher mortality, although in recent years, the mortality has been lowered to 3.8%; this procedure involves dissection of the parietal pleura and division of the pulmonary vessels, as well as en bloc resection of the lung, pleura, pericardium, and diaphragm, followed by reconstruction
  • EPP provides the best local control, because it removes the entire pleural sac along with the lung parenchyma
  • With surgery alone, the recurrence rate is very high, and most patients die after a few months; at least half of the patients who have local control with surgery have distant metastasis upon autopsy
  • In patients with the epithelioid type, if the patient is fit to tolerate a thoracotomy, the best option is still a thoracotomy and macroscopic clearance of the tumor as part of multimodality therapy


See the list below:

  • Chemotherapy alone is recommended for patients with stage I-IV disease who are not candidates for surgery and for patients with sarcomatoid histology
  • The mainstay of treatment is combination chemotherapy with pemetrexed and cisplatin [3]
  • Other combination therapies that have also been used are carboplatin and pemetrexed, which is beneficial in patients with poor performance status or who have comorbidities
  • Combination cisplatin and gemcitabine may be used if patients cannot take pemetrexed

First-line combination chemotherapy:

  • Pemetrexed 500 mg/m 2 IV on day 1 plus  cisplatin 75 mg/m 2; every 3wk [4, 5, 6] or
  • Pemetrexed 500 mg/m 2 IV on day 1 plus  carboplatin AUC 5; every 3wk [4, 7, 8] or
  • Gemcitabine 1000-1250 mg/m 2 IV on days 1, 8, and 15 plus  cisplatin 80-100 mg/m 2 on day 1; every 3-4wk [9, 10] or
  • Amatuximab 5 mg/kg on days 1 and 8 plus pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 of a 21-day cycle for up to six cycles.{17} 

Second-line chemotherapy:

  • Pemetrexed 500 mg/m 2 IV on day 1; every 3wk (if not used as first-line therapy) [11, 12] or
  • Vinorelbine 30 mg/m 2 IV weekly [13, 14]

Radiation therapy

Radiation therapy is recommended after surgery and/or in conjunction with chemotherapy. Generally, adjunctive radiation therapy should be given to patients after EPP.

Preoperative radiation therapy [1] :

  • Total dose: 45-50 Gy
  • Fraction size: 1.8-2 Gy
  • Treatment duration: 4-5wk

Postoperative radiation therapy or negative margins [1] :

  • Total dose: 50-54 Gy
  • Fraction size: 1.8-2 Gy
  • Treatment duration: 4-5wk

Microscopic-macroscopic positive margins [1] :

  • Total dose: 54-60 Gy
  • Fraction size: 1.8-2 Gy
  • Treatment duration: 5-6wk

Palliative radiation therapy or chest wall pain from recurrent nodules [1] :

  • Total dose: 20-24 Gy
  • Fraction size: 4 Gy or greater
  • Treatment duration: 1-2wk

Multiple brain or bone metastases [1] :

  • Total dose: 30 Gy
  • Fraction size: 3 Gy
  • Treatment duration: 2wk

Prophylactic radiation to prevent surgical tract recurrence [1] :

  • Total dose: 21 Gy
  • Fraction size: 7 Gy
  • Treatment duration: 1-2wk

Trimodality therapy

See the list below:

  • Trimodality therapy involves a combination of all 3 standard strategies (ie, surgery, chemotherapy, radiation) and is recommended for stage II-III disease that is operable and stage IV disease that is inoperable or in patients with sarcomatoid histology [1]
  • Different chemotherapeutic regimens found to be useful in the trimodality treatment include cyclophosphamide/ doxorubicin (Adriamycin)/cisplatin (CAP regimen), carboplatin/ paclitaxel (CP regimen), and cisplatin/ methotrexate/ vinblastine (CMV regimen)