Malignant Pleural Mesothelioma Treatment Protocols

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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
  

Stages II-III resectable:

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

Stages II-III unresectable:

• Chemotherapy is recommended
  

Stage IV:

• Chemotherapy
  
• 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]

• 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
  

Chemotherapy

• 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
  
• 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/m² IV on day 1 plus cisplatin 75 mg/m²; every 3wk^{[2, 3, 4]}or
  
• Pemetrexed 500 mg/m² IV on day 1 plus carboplatin AUC 5; every 3wk^{[2, 5, 6]}or
  
• Gemcitabine 1000-1250 mg/m² IV on days 1, 8, and 15 plus cisplatin 80-100 mg/m² on day 1; every 3-4wk^{[7, 8]}
  

Second-line chemotherapy:

• Pemetrexed 500 mg/m² IV on day 1; every 3wk (if not used as first-line therapy)^{[9, 10]}or
  
• Vinorelbine 30 mg/m² IV weekly^{[11, 12]}
  

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 ^[1]

• 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)