National Cancer Institute


Posted Date: Apr 27, 2014

Expert-reviewed information summary about the treatment of malignant mesothelioma.

Malignant Mesothelioma Treatment

General Information About Malignant Mesothelioma Treatment

Diagnosis and Prognostic Factors

Prognosis in this disease is difficult to assess consistently because there is great variability in the time before diagnosis and the rate of disease progression. In large retrospective series of pleural mesothelioma patients, important prognostic factors were found to be:

  • Stage.
  • Age.
  • Performance status.
  • Histology.

Follow-up and Survivorship

Various surgical procedures may be possible in selected patients, and they provide long-term survival without cure. For patients treated with aggressive surgical approaches, factors associated with improved long-term survival include the following:

  • Epithelial histology.
  • Negative lymph nodes.
  • Negative surgical margins.

For those patients treated with aggressive surgical approaches, nodal status is an important prognostic factor. Median survival has been reported as 16 months for patients with malignant pleural disease and 5 months for patients with extensive disease. In some instances the tumor grows through the diaphragm making the site of origin difficult to assess. Cautious interpretation of treatment results with this disease is imperative because of the selection differences among series. Effusions, both pleural and peritoneal, represent major symptomatic problems for at least 66% of the patients. (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.)

Carcinogenesis

A history of asbestos exposure is reported in about 70% to 80% of all cases of mesothelioma.

Cellular Classification of Malignant Mesothelioma

Histologically, these tumors are composed of fibrous or epithelial elements or both. The epithelial form occasionally causes confusion with peripheral anaplastic lung carcinomas or metastatic carcinomas. Attempts at diagnosis by cytology or needle biopsy of the pleura are often unsuccessful. It can be especially difficult to differentiate mesothelioma from adenocarcinoma on small tissue specimens. Thoracoscopy can be valuable in obtaining adequate tissue specimens for diagnostic purposes. Examination of the gross tumor at surgery and use of special stains or electron microscopy can often help. The special stains reported to be most useful include periodic acid-Schiff diastase, hyaluronic acid, mucicarmine, CEA, and Leu M1. Histologic appearance seems to be of prognostic value, and most clinical studies show that patients with epithelial mesotheliomas have a better prognosis than those with sarcomatous or mixed histology mesotheliomas.

Stage Information for Malignant Mesothelioma

Patients with stage I disease have a significantly better prognosis than those with more advanced stages. Because of the relative rarity of this disease, exact survival information based upon stage is limited.

Definitions of TNM

The American Joint Committee on Cancer has designated staging by TNM classification to define malignant mesothelioma.

International Mesothelioma Interest Group Staging System for Diffuse Malignant Pleural Mesothelioma

Treatment Option Overview

Standard treatment for all but localized mesothelioma is generally not curative. Although some patients will experience long-term survival with aggressive treatment approaches, it remains unclear if overall survival (OS) has been significantly altered by the different treatment modalities or by combinations of modalities. Extrapleural pneumonectomy in selected patients with early stage disease may improve recurrence-free survival, but its impact on OS is unknown. Pleurectomy and decortication can provide palliative relief from symptomatic effusions, discomfort caused by tumor burden, and pain caused by invasive tumor. (Refer to the PDQ summary on Pain for more information.) Operative mortality from pleurectomy/decortication is less than 2%, while mortality from extrapleural pneumonectomy has ranged from 6% to 30%.

The addition of radiation therapy and/or chemotherapy following surgical intervention has not demonstrated improved survival. The use of radiation therapy in pleural mesothelioma has been shown to alleviate pain in the majority of patients treated; however, the duration of symptom control is short-lived. Single-agent and combination chemotherapy have been evaluated in single and combined modality studies. The most studied agent is doxorubicin, which has produced partial responses in approximately 15% to 20% of patients studied. Some combination chemotherapy regimens have been reported to have higher response rates in small phase II trials; however, the toxic effects reported are also higher, and there is no evidence that combination regimens result in longer survival or longer control of symptoms..

Recurrent pleural effusions may be treated with pleural sclerosing procedures; however, failure rates are usually secondary to the bulk of the tumor, which precludes pleural adhesion due to the inability of the lung to fully expand.

Localized Malignant Mesothelioma (Stage I)

Standard treatment options:

Treatment options under clinical evaluation:

  • Palliative surgery (i.e., pleurectomy and decortication) with or without postoperative radiation therapy.
  • Extrapleural pneumonectomy.
  • Palliative radiation therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with localized malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Advanced Malignant Mesothelioma (Stages II, III, and IV)

Standard treatment options:

A large, randomized study from the United Kingdom (BTS-MRC-MS01) compared active symptom control (ASC) with the chemotherapy regimens of mitomycin C, vinblastine, and cisplatin (MVP) or single-agent vinorelbine. The trial was sized to detect a difference of 9 to 12 months in median survival with a total of 840 patients. As a result of slow accrual, the two chemotherapy regimens were collapsed, and the statistical plan revised. In a total of 409 patients, no significant difference in survival was detected between ASC and chemotherapy.[Level of evidence: 1iiA]

Many phase II trials of chemotherapy have been reported. The safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery was demonstrated in a randomized phase III trial.[Level of evidence: 1iiA] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously every 21 days). With a total of 456 enrolled patients in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy. After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects. Folic acid (350–1,000 µg orally) was given daily, beginning 1 to 3 weeks before the first chemotherapy dose and continuing daily until 1 to 3 weeks after treatment ended. A vitamin B12 injection (1,000 µg intramuscularly) was administered 1 to 3 weeks before the first chemotherapy dose and was repeated approximately every 9 weeks until treatment ended. Dexamethasone (4 mg) or an equivalent corticosteroid was administered orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

In an analysis of all patients who were randomly assigned and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone; the median survivals were 12.1 versus 9.3 months, respectively (P = .020). The hazard ratio for death of patients in the pemetrexed plus cisplatin arm versus those in the control arm was 0.77. Median time-to-progression was significantly longer in the pemetrexed plus cisplatin arm (5.7 months vs. 3.9 months, P = .001). This superiority in the combination arm was also demonstrated in the vitamin-supplemented subgroup. The median survivals were 13.3 and 10.0 months in the combination group and cisplatin alone group, respectively (P = .051). The principal adverse effects of the pemetrexed plus cisplatin regimen were myelosuppression, fatigue, nausea, vomiting, and dyspnea. Most grade 3 to 4 adverse effects were significantly reduced by vitamin supplementation without any decrease in efficacy.

A randomized, phase III trial of 250 patients, was performed by the European Organisation for Research and Treatment of Cancer (EORTC-08983) to compare cisplatin alone with the combination of raltitrexed, a thymidine synthase inhibitor, and cisplatin in first-line treatment of patients with malignant pleural mesothelioma. Cisplatin (80 mg/m2 IV) was given on day 1, alone or combined with raltitrexed (3 mg/m2). No toxic deaths resulted, and the main grade 3 or 4 toxicities observed were neutropenia and emesis, which were reported twice as often in the combination arm. Among 213 patients with measurable disease, the response rate was 13.6% versus 23.6%, respectively (P = .056). No difference in quality of life was observed. The combination arm was associated with an increased survival. Median overall and 1-year survival were 8.8 versus 11.4 months, respectively and 40% versus 46%, respectively (P = .048).[Level of evidence: 1iiA]

Malignant Peritoneal Mesothelioma

A multi-institutional, registry study evaluated cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse, malignant peritoneal mesothelioma. Among 401 patients, 187 (46%) had complete or near-complete cytoreduction, and 372 (92%) received HIPEC. Of the HIPEC patients, 311 (83%) received cisplatin and doxorubicin. The median follow-up period was 33 months (range, 1–235 months). Grade 3 to 4 complications were seen in 127 (31%) of the 401 patients, and 9 patients (2%) died perioperatively.

The mean length of hospital stay was 22 days (standard deviation, 15 days). The overall median survival was 53 months (1–235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis:

  • Epithelial subtype (P < .001).
  • Absence of lymph node metastasis (P < .001).
  • Completeness of cytoreduction (CC) scores of CC-0 or CC-1 (P < .001).
  • HIPEC (P = .002).

This kind of analysis is subject to the biases of strong patient selection.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with advanced malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Recurrent Malignant Mesothelioma

Treatment of patients with recurrent mesothelioma usually utilizes procedures and/or agents not previously employed in the initial treatment attempt. No standard treatment approaches have been proven to improve survival or control symptoms for a prolonged period of time. These patients should be considered candidates for phase I and II clinical trials evaluating new biologicals, chemotherapeutic agents, or physical approaches. Patients with recurrent mesothelioma who have not received prior chemotherapy are candidates for first-line chemotherapy with cisplatin pemetrexed or cisplatin raltitrexed. (Refer to the Advanced Malignant Mesothelioma (Stages II, III, and IV) section of this summary.) However, patients with recurrent mesothelioma who receive surgery, or at least do not receive chemotherapy as part of the primary treatment and recur subsequently, are candidates for chemotherapy.

A large, randomized study compared pemetrexed to best supportive care in 243 patients who received one prior regimen of chemotherapy that did not include pemetrexed.[Level of evidence: 1iiA] No survival benefit was shown in patients who received pemetrexed, although the progression-free survival rate, time-to-progression, and the response rates favored the pemetrexed arm.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Changes to This Summary (03/07/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Malignant Mesothelioma Treatment

Editorial changes were made to this section.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of malignant mesothelioma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Malignant Mesothelioma Treatment are:

  • Janet Dancey, MD, FRCPC (Ontario Institute for Cancer Research & NCIC Clinical Trials Group)
  • Patrick Forde, MD (Johns Hopkins University)
  • Giuseppe Giaccone, MD, PhD (National Cancer Institute)
  • Raymond Mak, MD

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Malignant Mesothelioma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/malignantmesothelioma/HealthProfessional. Accessed <MM/DD/YYYY>.

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

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Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

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