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Malignant Mesothelioma - Information for Health professionals

General Information

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, and histology.[1][2] 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 epithelial histology, negative lymph nodes, and negative surgical margins.[3][4] For those patients treated with aggressive surgical approaches, nodal status is an important prognostic factor.[3] 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.) A history of asbestos exposure is reported in about 70% to 80% of all cases of mesothelioma.[1][5][6]

References:

  1. Ruffie P, Feld R, Minkin S, et al.: Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. J Clin Oncol 7 (8): 1157-68, 1989.

  2. Tammilehto L, Maasilta P, Kostiainen S, et al.: Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of sixty-five patients. Respiration 59 (3): 129-35, 1992.

  3. Sugarbaker DJ, Strauss GM, Lynch TJ, et al.: Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 11 (6): 1172-8, 1993.

  4. Sugarbaker D, Harpole D, Healey E, et al.: Multimodality treatment of malignant pleural mesothelioma (MPM): results in 94 consecutive patients. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1083, 356, 1995.

  5. Chailleux E, Dabouis G, Pioche D, et al.: Prognostic factors in diffuse malignant pleural mesothelioma. A study of 167 patients. Chest 93 (1): 159-62, 1988.

  6. Adams VI, Unni KK, Muhm JR, et al.: Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 cases. Cancer 58 (7): 1540-51, 1986.

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Cellular Classification

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.[1] 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.[2] 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.[2][3][4]

References:

  1. Boutin C, Rey F: Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: Diagnosis. Cancer 72 (2): 389-93, 1993.

  2. Chahinian AP, Pass HI: Malignant mesothelioma. In: Holland JC, Frei E, eds.: Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc, 2000, pp 1293-1312.

  3. Nauta RJ, Osteen RT, Antman KH, et al.: Clinical staging and the tendency of malignant pleural mesotheliomas to remain localized. Ann Thorac Surg 34 (1): 66-70, 1982.

  4. Sugarbaker DJ, Strauss GM, Lynch TJ, et al.: Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 11 (6): 1172-8, 1993.

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Stage Information

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.[1] A proposed staging system based upon thoracic surgery principles and clinical data is shown below.[2] It is a modification of the older system proposed by Butchart et al.[3] Other staging systems that have been employed, including the current international TNM staging system, are summarized by the International Mesothelioma Interest Group.[4]

  • Stage I: Disease confined within the capsule of the parietal pleura (i.e., ipsilateral pleura, lung, pericardium, and diaphragm).
  • Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes.
  • Stage III: Local extension of disease into the following areas, e.g., chest wall or mediastinum, heart or through the diaphragm or peritoneum, with or without extrathoracic or contralateral (N3) lymph node involvement.
  • Stage IV: Distant metastatic disease.

Localized malignant mesothelioma

See description of stage I above.

Advanced malignant mesothelioma

See descriptions of stages II, III, and IV above.

For the purposes of the discussion of treatment in this summary, the disease is categorized as either localized or advanced.

References:

  1. Chahinian AP, Pass HI: Malignant mesothelioma. In: Holland JC, Frei E, eds.: Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc, 2000, pp 1293-1312.

  2. Sugarbaker DJ, Strauss GM, Lynch TJ, et al.: Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 11 (6): 1172-8, 1993.

  3. Butchart EG, Ashcroft T, Barnsley WC, et al.: Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 31 (1): 15-24, 1976.

  4. Rusch VW: A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest 108 (4): 1122-8, 1995.

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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 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 overall survival is unknown.[1] Pleurectomy and decortication can provide palliative relief from symptomatic effusions, discomfort caused by tumor burden, and pain caused by invasive tumor. Operative mortality from pleurectomy/decortication is less than 2%,[2] while mortality from extrapleural pneumonectomy has ranged from 6% to 30%.[1][3] The addition of radiation therapy and/or chemotherapy following surgical intervention has not demonstrated improved survival.[2] 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.[4][5] 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.[6] 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.[6][7]. 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.

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

References:

  1. Rusch VW, Piantadosi S, Holmes EC: The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial. J Thorac Cardiovasc Surg 102 (1): 1-9, 1991.

  2. Rusch V, Saltz L, Venkatraman E, et al.: A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol 12 (6): 1156-63, 1994.

  3. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al.: Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma. Chest 103 (4 Suppl): 377S-381S, 1993.

  4. Bissett D, Macbeth FR, Cram I: The role of palliative radiotherapy in malignant mesothelioma. Clin Oncol (R Coll Radiol) 3 (6): 315-7, 1991.

  5. Ball DL, Cruickshank DG: The treatment of malignant mesothelioma of the pleura: review of a 5-year experience, with special reference to radiotherapy. Am J Clin Oncol 13 (1): 4-9, 1990.

  6. Weissmann LB, Antman KH: Incidence, presentation and promising new treatments for malignant mesothelioma. Oncology (Huntingt) 3 (1): 67-72; discussion 73-4, 77, 1989.

  7. Ong ST, Vogelzang NJ: Chemotherapy in malignant pleural mesothelioma. A review. J Clin Oncol 14 (3): 1007-17, 1996.

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Localized Malignant Mesothelioma (Stage I)

Standard treatment options:[1]

  1. Solitary mesotheliomas: Surgical resection en bloc including contiguous structures to ensure wide disease-free margins. Sessile polypoid lesions should be treated with surgical resection to ensure maximal potential for cure.[2]
  2. Intracavitary mesothelioma:
    • Palliative surgery (i.e., pleurectomy and decortication) with or without postoperative radiation therapy.
    • Extrapleural pneumonectomy.
    • Palliative radiation therapy.

Treatment options under clinical evaluation:

  1. Intracavitary chemotherapy following resection.[3][4]
  2. Multimodality therapy.[4][5][6]
  3. Other clinical trials.

Information about ongoing clinical trials is available from the NCI Web site.

References:

  1. Antman KH, Li FP, Osteen R, et al.: Mesothelioma. Cancer: Principles and Practice of Oncology Updates 3(1): 1-16, 1989.

  2. Martini N, McCormack PM, Bains MS, et al.: Pleural mesothelioma. Ann Thorac Surg 43 (1): 113-20, 1987.

  3. Markman M, Kelsen D: Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 118 (7): 547-50, 1992.

  4. Rusch V, Saltz L, Venkatraman E, et al.: A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol 12 (6): 1156-63, 1994.

  5. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al.: Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma. Chest 103 (4 Suppl): 377S-381S, 1993.

  6. Vogelzang NJ: Malignant mesothelioma: diagnostic and management strategies for 1992. Semin Oncol 19 (4 Suppl 11): 64-71, 1992.

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

Standard treatment options:

  1. Symptomatic treatment to include drainage of effusions, chest tube pleurodesis, or thoracoscopic pleurodesis.[1]
  2. Palliative surgical resection in selected patients.[2][3]
  3. Palliative radiation therapy.[4][5]
  4. Single-agent chemotherapy. Partial responses have been reported with doxorubicin, epirubicin, mitomycin, cyclophosphamide, cisplatin, carboplatin, and ifosfamide.[6][7][8]
  5. Combination chemotherapy (under clinical evaluation).[6][7][9] Information about ongoing clinical trials is available from the NCI Web site.
  6. Multimodality clinical trials.[10][11][12][13][14]
  7. Intracavitary therapy. Intrapleural or intraperitoneal administration of chemotherapeutic agents (e.g., cisplatin, mitomycin, and cytarabine) has been reported to produce transient reduction in the size of tumor masses and temporary control of effusions in small clinical studies.[15][16][17] Additional studies are needed to define the role of intracavitary therapy.

Many phase II trials of chemotherapy have been reported.[6][7][9] 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.[18][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 randomized 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.

References:

  1. Boutin C, Viallat JR, Rey R: Thoracoscopy in Diagnosis, Prognosis and Treatment of Mesothelioma. In: Antman K, Aisner J, eds.: Asbestos-Related Malignancy. Orlando,Fla: Grune & Stratton, 1987, pp 301-21.

  2. Butchart EG, Ashcroft T, Barnsley WC, et al.: The role of surgery in diffuse malignant mesothelioma of the pleura. Semin Oncol 8 (3): 321-8, 1981.

  3. Martini N, McCormack PM, Bains MS, et al.: Pleural mesothelioma. Ann Thorac Surg 43 (1): 113-20, 1987.

  4. Bissett D, Macbeth FR, Cram I: The role of palliative radiotherapy in malignant mesothelioma. Clin Oncol (R Coll Radiol) 3 (6): 315-7, 1991.

  5. Ball DL, Cruickshank DG: The treatment of malignant mesothelioma of the pleura: review of a 5-year experience, with special reference to radiotherapy. Am J Clin Oncol 13 (1): 4-9, 1990.

  6. Chahinian AP, Antman K, Goutsou M, et al.: Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B. J Clin Oncol 11 (8): 1559-65, 1993.

  7. Ong ST, Vogelzang NJ: Chemotherapy in malignant pleural mesothelioma. A review. J Clin Oncol 14 (3): 1007-17, 1996.

  8. Lerner HJ, Schoenfeld DA, Martin A, et al.: Malignant mesothelioma. The Eastern Cooperative Oncology Group (ECOG) experience. Cancer 52 (11): 1981-5, 1983.

  9. Andreopoulou E, Ross PJ, O'Brien ME, et al.: The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant mesothelioma. Ann Oncol 15 (9): 1406-12, 2004.

  10. Mattson K, Holsti LR, Tammilehto L, et al.: Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation. Int J Radiat Oncol Biol Phys 24 (4): 643-50, 1992.

  11. Weissmann LB, Antman KH: Incidence, presentation and promising new treatments for malignant mesothelioma. Oncology (Huntingt) 3 (1): 67-72; discussion 73-4, 77, 1989.

  12. Vogelzang NJ: Malignant mesothelioma: diagnostic and management strategies for 1992. Semin Oncol 19 (4 Suppl 11): 64-71, 1992.

  13. Sugarbaker D, Harpole D, Healey E, et al.: Multimodality treatment of malignant pleural mesothelioma (MPM): results in 94 consecutive patients. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1083, 356, 1995.

  14. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al.: Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma. Chest 103 (4 Suppl): 377S-381S, 1993.

  15. Markman M, Kelsen D: Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 118 (7): 547-50, 1992.

  16. Markman M, Cleary S, Pfeifle C, et al.: Cisplatin administered by the intracavitary route as treatment for malignant mesothelioma. Cancer 58 (1): 18-21, 1986.

  17. Rusch VW, Figlin R, Godwin D, et al.: Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial. J Clin Oncol 9 (2): 313-9, 1991.

  18. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al.: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21 (14): 2636-44, 2003.

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Recurrent Malignant Mesothelioma

Treatment of 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.[1][2][3][4][5] Information about ongoing clinical trials is available from the NCI Web site.

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 large phase III randomized trial.[6][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 randomized 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.

References:

  1. Rusch V, Saltz L, Venkatraman E, et al.: A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol 12 (6): 1156-63, 1994.

  2. Markman M, Kelsen D: Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 118 (7): 547-50, 1992.

  3. Weissmann LB, Antman KH: Incidence, presentation and promising new treatments for malignant mesothelioma. Oncology (Huntingt) 3 (1): 67-72; discussion 73-4, 77, 1989.

  4. Boutin C, Viallat JR, Van Zandwijk N, et al.: Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma. Cancer 67 (8): 2033-7, 1991.

  5. Ong ST, Vogelzang NJ: Chemotherapy in malignant pleural mesothelioma. A review. J Clin Oncol 14 (3): 1007-17, 1996.

  6. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al.: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21 (14): 2636-44, 2003.

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Changes to This Summary (08/23/2007)

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.

Editorial changes were made to this summary.

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This information was last updated on August 23, 2007