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 Malignant Pleural Mesothelioma Treatment Protocols

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Malignant Pleural Mesothelioma Treatment Protocols

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Treatment Protocols

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

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
    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

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)

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