Malignant Pleural Mesothelioma Treatment Protocols
Updated: Nov 17, 2023
Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD
Treatment protocols for malignant pleural mesothelioma are provided below, including the following:
Stages I-III resectable, with epithelial histology:
Induction chemotherapy (cisplatin [or carboplatin] and pemetrexed) followed by surgical exploration or
Pleurectomy/decortication (P/D) with adjuvant chemotherapy, optionally followed by radiation therapy or
Extrapleural pneumonectomy (EPP) with sequential chemotherapy plus hemithoracic radiation therapy
Stages I-III unresectable:
Chemotherapy is recommended
Radiation for palliation and positive margins
Stage IV or sarcomatoid or mixed histology :
Nivolumab plus ipilimumab
Radiation post chemotherapy for palliation
Surgery is not recommended for patients with stage IV disease
The 2 surgical procedures commonly used in malignant mesothelioma are P/D and EPP. P/D 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%
P/D is a good option for patients with early-stage disease with favorable histology and fpr good-risk patients. In addition, P/D is appropriate for patients with advanced disease and mixed histology and/or high risk.[3, 4]
EPP is a more extensive procedure than P/D; it 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 the entire pleural sac is removed along with the lung parenchyma. Mortality is higher with EPP than with P/D, although in recent years, the mortality in EPP has been lowered to 3.8%
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 for stage IV disease is combination therapy with ipilimumab and nivolumab.
For patients who cannot receive immunotherapy, chemotherapy with cisplatin and pemetrexed is an option.[5]
Carboplatin plus pemetrexed can be used in patients unlikely to tolerate cisplatin, due to poor performance status or comorbidities.
Cisplatin plus gemcitabine may be used in patients who cannot take pemetrexed.
Hyperthermic intrathoracic chemotherapy (HITHOC) with cisplatin alone or combined with doxorubicin or gemcitabine has demonstrated benefit[6]
First-line combination chemotherapy:
Nivolumab 360 mg IV q3Weeks plusipilimumab 1 mg/kg IV q6Weeks; continue combination until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression[7, 8, 9] or
Pemetrexed 500 mg/m2 IV pluscisplatin 75 mg/m2 IV plusbevacizumab 15 mg/kg IV every 3 weeks for six cycles, with bevacizumab maintainence until progression[3] or
Pemetrexed 500 mg/m2 IV pluscarboplatin AUC 5 IV (see also the Carboplatin AUC Dose Calculation [Calvert formula] calculator) plus bevacizumab 15 mg/kg IV every 3 weeks for six cycles, with bevacizumab maintainence until progression[3] or
Pemetrexed 500 mg/m2 IV plus cisplatin 75 mg/m2 IV every 3 weeks[10, 11, 12] or
Pemetrexed 500 mg/m2 IV plus carboplatin AUC 5 IV every 3 weeks[10, 13, 14] or
Gemcitabine 1000-1250 mg/m2 IV on Days 1, 8, and 15 plus cisplatin 80-100 mg/m2 IV on Day 1 every 3-4 weeks[15, 16]
Second-line chemotherapy
The following regimens are used for second-line therapy if they were not used for first-line treatment:
Nivolumab 360 mg IV q3Weeks plusipilimumab 1 mg/kg IV q6Weeks (if not used as first-line therapy); continue combination until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression[7, 8]
Pemetrexed 500 mg/m2 IV on day 1 every 3 weeks[17, 18] or
Pemetrexed 500 mg/m2 IV plus cisplatin 75 mg/m2 IV every 3 weeks[10, 11, 12] or
Pemetrexed 500 mg/m2 IV pluscisplatin 75 mg/m2 IV plusbevacizumab 15 mg/kg IV every 3 weeks for six cycles, with bevacizumab maintainence until progression[3] or
Vinorelbine 30 mg/m2 IV weekly[19, 20]
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[3] :
Postoperative radiation therapy or negative margins[3] :
Microscopic-macroscopic positive margins[3] :
Palliative radiation therapy or chest wall pain from recurrent nodules[3] :
Multiple brain or bone metastases[3] :
Prophylactic radiation to help prevent surgical tract recurrence[3] :
Trimodality therapy involves a combination of all 3 standard strategies (ie, surgery, chemotherapy, radiation) and is recommended for stage II-III disease that is medically operable and has epithelial histology.[3, 2]
Chemotherapeutic regimens found to be useful in the trimodality treatment include the following: