Skip to main content
Log in

Current therapy for malignant mesothelioma

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

This review briefly summarizes the results of previous systemic (chemotherapy) and local (surgery and radiotherapy) treatment attempted to date for malignant mesothelioma. The prospects for newer modalities, ie molecular and biologic therapies, are also highlighted, including results of both preclinical and early clinical research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Peto J, Hodgson JT, Matthews FE, Jones JR: Continuing increase in mesothelioma mortality in Britain. Lancet 1995, 345:535–539.

    Article  PubMed  CAS  Google Scholar 

  2. Testa JR, Carbone M, Hirvonen A, et al.: A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas. Cancer Res 1998, 58:4505–4509.

    PubMed  CAS  Google Scholar 

  3. Kawai A, Nagasaka Y, Muraki M, et al.: Brain metastasis in malignant pleural mesothelioma. Intern Med 1997, 36:591–594.

    PubMed  CAS  Google Scholar 

  4. Ruiz HG, Garcia GT, Azagra RP, et al.: Pelvic and lumbar metastasis detected by bone scintigraphy in malignant pleural mesothelioma. Nuklearmedizin 1999, 38:68–71.

    Google Scholar 

  5. Baas P, van Meerbeeck J, Groen H, et al.: Caelyx (TM) in malignant mesothelioma: a phase II EORTC study. Ann Oncol 2000, 11:697–700.

    Article  PubMed  CAS  Google Scholar 

  6. Lerner HJ, Schoenfeld DA, Martin A, et al.: Malignant mesothelioma: the Eastern Cooperative Oncology Group (ECOG) experience. Cancer 1983, 52:1981–1985.

    Article  PubMed  CAS  Google Scholar 

  7. Colbert N, Vannetzel JM, Izrael V, et al.: A prospective study of detorubicin in malignant mesothelioma. Cancer 1985, 56:2170–2174.

    Article  PubMed  CAS  Google Scholar 

  8. Kindler HL, van Meerbeeck JP: The role of gemcitabine in the treatment of malignant mesothelioma. Semin Oncol 2002, 29:70–76.

    Article  PubMed  CAS  Google Scholar 

  9. van Meerbeeck JP, Bass P, Debruyne C, et al.: A phase II study of gemcitabine in patients with malignant pleural mesothelioma. Cancer 1999, 85:2577–2582.

    Article  PubMed  Google Scholar 

  10. Bischoff HG, Manegold C, Knopp M, et al.: Gemcitabine may reduce tumor load and tumor associated symptoms in malignant pleural mesothelioma. [abstract]. Proc ASCO 1998, 17:464a.

    Google Scholar 

  11. Baas P: Chemotherapy for malignant mesothelioma: from doxorubicin to vinorelbine. Semin Oncol 2002, 29:62–69.

    Article  PubMed  CAS  Google Scholar 

  12. Mbidde EK, Smith IE, Harland S: Phase II trial of carboplatin (Jm8) in the treatment of patients with mesothelioma (M). Br J Cancer 1986, 54:215–216.

    Google Scholar 

  13. Vogelzang NJ, Goutsou M, Corson JM, et al.: Carboplatin in malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B. Cancer Chemother Pharmacol 1990, 27:239–242.

    Article  PubMed  CAS  Google Scholar 

  14. Steele JP, John W, Vogelzang NJ: Phase II trial of vinorelbine and oxaliplatin in malignant pleural mesothelioma [abstract]. Proc ASCO 1999, 18:1844a.

    Google Scholar 

  15. Fizazi K, John WJ, Vogelzang NJ: The emerging role of antifolates in the treatment of malignant pleural mesothelioma. Semin Oncol 2002, 29:77–81.

    Article  PubMed  CAS  Google Scholar 

  16. Umsawasdi T, Dhingra HM, Charnsangavej C, Luna MA: A case report of malignant pleural mesothelioma with long-term disease control after chemotherapy. Cancer 1991, 67:48–54.

    Article  PubMed  CAS  Google Scholar 

  17. Colleoni M, Liessi G, Avventi C, et al.: Response to chemotherapy of brain metastases from malignant pleural mesothelioma. Tumori 1996, 82:456–458.

    PubMed  CAS  Google Scholar 

  18. Dimitrov NV, Egner J, Balcueva E, Suhrland LG: High-dose methotrexate with citrovorum factor and vincristine in the treatment of malignant mesothelioma. Cancer 1982, 50:1245–1247.

    Article  PubMed  CAS  Google Scholar 

  19. Djerassi I, Kim JS, Reggev A: Response of astrocytoma to highdose methotrexate with citrovorum factor rescue. Cancer 1985, 55:2741–2747.

    Article  PubMed  CAS  Google Scholar 

  20. Solheim OP, Saeter G, Finnanger AM, Stenwig AE: High-dose methotrexate in the treatment of malignant mesothelioma of the pleura: a phase II study. Br J Cancer 1992, 65:956–960.

    PubMed  CAS  Google Scholar 

  21. Vogelzang NJ, Weissman LB, Herndon JE, et al.: Trimetrexate in malignant mesothelioma: a Cancer and Leukemia Group B phase II study. J Clin Oncol 1994, 12:1436–1442.

    PubMed  CAS  Google Scholar 

  22. Kindler HL, Belani CP, Herndon JE, et al.: Edatrexate (10-ethyldeaza-aminopterin) (NSC #626715) with or without leucovorin rescue for malignant mesothelioma: sequential phase II trials by the Cancer and Leukemia Group B. Cancer 1999, 86:1985–1991.

    Article  PubMed  CAS  Google Scholar 

  23. Halme M, Knuuttila A, Vehmas T, et al.: High-dose methotrexate in combination with interferons in the treatment of malignant pleural mesothelioma. Br J Cancer 1999, 80:1781–1785.

    Article  PubMed  CAS  Google Scholar 

  24. Brodin O, Knuuttila A, Halme H: Combined treatment of malignant mesothelioma of the pleura with high dose methotrexate and interferon alfa and gamma [abstract]. Br J Cancer 1999, 80:1781–1985.

    Article  CAS  Google Scholar 

  25. Upham JW, Musk AW, van-Hagel G: Interferon alpha and doxorubicin in malignant mesothelioma: a phase II study. Aust NZ J Med 1993, 2316:683–687.

    Google Scholar 

  26. Carmichael J, Degraff WG, Gamson J, et al.: Radiation sensitivity of human lung cancer cell lines. Eur J Cancer Clin Oncol 1989, 25:527–534.

    Article  PubMed  CAS  Google Scholar 

  27. Boutin C, Rey F, Viallat JR: Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma: a randomized trial of local radiotherapy. Chest 1995, 108:754–758.

    PubMed  CAS  Google Scholar 

  28. Kutcher GJ, Kestler C, Greenblatt D, et al.: Technique for external beam treatment for mesothelioma. Int J Radiat Oncol Biol Physics 1987, 13:1747–1752.

    CAS  Google Scholar 

  29. Sauter ER, Langer C, Coia LR, et al.: Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation. J Surg Oncol 1995, 60:100–105.

    Article  PubMed  CAS  Google Scholar 

  30. Soubra M, Dunscombe PB, Hodson DI, Wong G: Physical aspects of external beam radiotherapy for the treatment of malignant pleural mesothelioma. Int J Radiat Oncol Biol Physics 1990, 18:1521–1527.

    CAS  Google Scholar 

  31. Baldini EH, Recht A, Strauss GM, et al.: Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1997, 63:334–338.

    Article  PubMed  CAS  Google Scholar 

  32. 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 1994, 12:1156–1163.

    PubMed  CAS  Google Scholar 

  33. Rusch VW, Rosenzweig K, Venkatraman E, et al.: A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2001, 122:788–795. This MSKCC study demonstrated the potential efficacy of radiotherapy.

    Article  PubMed  CAS  Google Scholar 

  34. Sugarbaker DJ, Flores RM, Jaklitsch MT, et al.: Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999, 117:54–63. This landmark paper demonstrated improved survival in patients with epithelial histology, negative mediastinal nodes, and complete surgical resection.

    Article  PubMed  CAS  Google Scholar 

  35. Eisbruch A, Ten Haken RK, Kim HM, et al.: Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Physics 1999, 45:577–587. One of two important trials of intensity-modulated radiotherapy.

    Article  CAS  Google Scholar 

  36. Zelefsky MJ, Fuks Z, Happersett L, et al.: Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol 2000, 55:241–249. One of two important trials of intensity-modulated radiotherapy.

    Article  PubMed  CAS  Google Scholar 

  37. Ahamad A, Forster R, Smythe R, et al.: IMRT for adjuvant treatment of malignant mesothelioma [abstract]. American Society of Therapeutic Radiology and Oncology, San Francisco, 2001.

  38. Noppen M, DeGreve J, Mignolet M, Vincken W: A prospective, randomised study comparing the efficacy of talc slurry and bleomycin in the treatment of malignant pleural effusions. Acta Clinica Belgica 1997, 52:258–262.

    PubMed  CAS  Google Scholar 

  39. Senyigit A, Yaramis A, Gurkan F, et al.: Pulmonary alveolar microlithiasis: a rare familial inheritance with report of six gases in a family: contribution of six new cases to the number of case reports in Turkey. Respiration 2001, 68:204–209.

    Article  PubMed  CAS  Google Scholar 

  40. Nasreen N, Mohammed KA, Dowling PA, et al.: Talc induces apoptosis in human malignant mesothelioma cells in vitro. Am J Respir Crit Care Med 2000, 161:595–600.

    PubMed  CAS  Google Scholar 

  41. Merritt N, Blewett C, Miller JD, et al.: Survival after conservative (palliative) management of pleural malignant mesothelioma. J Surg Oncol 2001, 78:171–174.

    Article  PubMed  CAS  Google Scholar 

  42. Martin-Ucar AE, Edwards JG, Rengajaran A, et al.: Palliative surgical debulking in malignant mesothelioma: predictors of survival and symptom control. Eur J Cardiothorac Surg 2001, 20:1117–1121.

    Article  PubMed  CAS  Google Scholar 

  43. Rusch VW: Pleurectomy/decortication and adjuvant therapy for malignant mesothelioma. Chest 1993, 103:S382-S384.

    Article  Google Scholar 

  44. 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 1991, 102:1–9.

    PubMed  CAS  Google Scholar 

  45. Butchart EG, Ashcroft T, Barnsley WC, Holden MP: Pleuropneumonectomy in management of diffuse malignant mesothelioma of pleura: experience with 29 patients. Thorax 1976, 31:15–24.

    PubMed  CAS  Google Scholar 

  46. Rusch VW, Venkatraman ES: Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. Ann Thorac Surg 1999, 68:1799–1804. The mortality rate in this study proved to be lower than expected.

    Article  PubMed  CAS  Google Scholar 

  47. 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 1994, 12:1156–1163.

    PubMed  CAS  Google Scholar 

  48. Rice TW, Adelstein DJ, Kirby TJ, et al.: Aggressive multimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1994, 58:24–29.

    Article  PubMed  CAS  Google Scholar 

  49. Juturi J, Adelstein DJ, Rice tea: intracavitary paclitaxel in the multimodality management of malignant pleural mesothelioma [abstract]. Proc ASCO 2001, 20:366a.

    Google Scholar 

  50. Ratto GB, Civalleri D, Esposito M, et al.: Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study. J Thorac Cardiovasc Surg 1999, 117:759–765.

    Article  PubMed  CAS  Google Scholar 

  51. Zellos LS, Sugarbaker DJ: Multimodality treatment of diffuse malignant pleural mesothelioma. Semin Oncol 2002, 29:41–50.

    Article  PubMed  Google Scholar 

  52. Pass HI, Temeck BK, Kranda K, et al.: Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma. Ann Surg Oncol 1997, 4:628–633.

    Article  PubMed  CAS  Google Scholar 

  53. Moskal TL, Dougherty TJ, Urschel JD, et al.: Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up. Ann Thorac Surg 1998, 66:1128–1133.

    Article  PubMed  CAS  Google Scholar 

  54. Sandberg AA, Bridge JA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: mesothelioma. Cancer Genet Cytogenet 2001, 127:93–110.

    Article  PubMed  CAS  Google Scholar 

  55. Kettunen E, Nissen AM, Ollikainen T, et al.: Gene expression profiling of malignant mesothelioma cell lines: cDNA array study. Int J Cancer 2001, 91:492–496.

    Article  PubMed  CAS  Google Scholar 

  56. Sun X, Dobra K, Bjornstedt M, Hjerpe A: Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells. Differentiation 2000, 66:181–188.

    Article  PubMed  CAS  Google Scholar 

  57. Ascoli V, Aalto Y, Carnovale-Scalzo C, et al.: DNA copy number changes in familial malignant mesothelioma. Cancer Genet Cytogenet 2001, 127:80–82.

    Article  PubMed  CAS  Google Scholar 

  58. Taguchi T, Jhanwar SC, Siegfried JM, et al.: Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res 1993, 53:4349–4355.

    PubMed  CAS  Google Scholar 

  59. Cheng JQ, Jhanwar SC, Klein WM, et al.: p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res 1994, 54:5547–5551.

    PubMed  CAS  Google Scholar 

  60. Strickler HD: A multicenter evaluation of assays for detection of SV40 DNA and results in masked mesothelioma specimens. Cancer Epidemiol Biomarkers Prev 2001, 10:523–532.

    PubMed  CAS  Google Scholar 

  61. Cicala C, Pompetti F, Carbone M: SV40 induces mesotheliomas in hamsters. Am J Pathol 1993, 142:1524–1533.

    PubMed  CAS  Google Scholar 

  62. Smythe WR, Hwang HC, Amin KM, et al.: Use of recombinant adenovirus to transfer the herpes simplex virus thymidine kinase (HSVtk) gene to thoracic neoplasms: an effective in vitro drug sensitization system. Cancer Res 1994, 54:2055–2059.

    PubMed  CAS  Google Scholar 

  63. Smythe WR, Hwang HC, Elshami AA, et al.: Treatment of experimental human mesothelioma using adenovirus transfer of the herpes simplex thymidine kinase gene. Ann Surg 1995, 222:78–86.

    Article  PubMed  CAS  Google Scholar 

  64. Sterman DH, Treat J, Litzky LA, et al.: Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma. Hum Gene Ther 1998, 9:1083–1092. The first clinical trial using a gene therapy approach for mesothelioma.

    PubMed  CAS  Google Scholar 

  65. Frizelle SP, Rubins JB, Zhou JX, et al.: Gene therapy of established mesothelioma xenografts with recombinant p16INK4a adenovirus. Cancer Gene Ther 2000, 7:1421–1425.

    Article  PubMed  CAS  Google Scholar 

  66. Pataer A, Smythe WR, Yu R, et al.: Adenovirus-mediated bak gene transfer induces apoptosis in mesothelioma cell lines. J Thorac Cardiovasc Surg 2001, 121:61–67.

    Article  PubMed  CAS  Google Scholar 

  67. Huang DC, Cory S, Strasser A: Bcl-2, Bcl-XL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death. Oncogene 1997, 14:405–414.

    Article  PubMed  CAS  Google Scholar 

  68. Narasimhan SR, Yang L, Gerwin BI, Broaddus VC: Resistance of pleural mesothelioma cell lines to apoptosis: relation to expression of Bcl-2 and Bax. Am J Physiol 1998, 275:L165-L171.

    PubMed  CAS  Google Scholar 

  69. Segers K, Ramael M, Singh SK, et al.: Immunoreactivity for bcl-2 protein in malignant mesothelioma and non-neoplastic mesothelium. Virchows Arch 1994, 424:631–634.

    Article  PubMed  CAS  Google Scholar 

  70. Leech SH, Olie RA, Gautschi O, et al.: Induction of apoptosis in lung-cancer cells following bcl-xL anti-sense treatment. Int J Cancer 2000, 86:570–576.

    Article  PubMed  CAS  Google Scholar 

  71. Schmitt E, Sane AT, Steyaert A, et al.: The Bcl-xL and Bax-alpha control points: modulation of apoptosis induced by cancer chemotherapy and relation to TPCK-sensitive protease and caspase activation. Biochem Cell Biol 1997, 75:301–314.

    Article  PubMed  CAS  Google Scholar 

  72. Cao XX, Mohiuddin I, Ece F, et al.: Histone deacetylase inhibitor down-regulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. Am J Respir Cell Mol Biol 2001, 25:562–568.

    PubMed  CAS  Google Scholar 

  73. Mohiuddin I, Cao X, Fang B, et al.: Significant augmentation of pro-apoptotic gene therapy by pharmacologic bcl-xl downr-regulation in mesothelioma. Cancer Gene Ther 2001, 8:547–554.

    Article  PubMed  CAS  Google Scholar 

  74. Smythe WR, Mohiuddin I, Cao X, Ozvaran M: Antisense therapy for malignant mesothelioma utilizing antisense oligonucleotides targeting the Bclxl gene product. J Thorac Cardiovasc Surg 2002, in press.

  75. Waheed I, Guo ZS, Chen GA, et al.: Antisense to SV40 early gene region induces growth arrest and apoptosis in T-antigen-positive human pleural mesothelioma cells. Cancer Res 1999, 59:6068–6073.

    PubMed  CAS  Google Scholar 

  76. Leigh RA, Webster I: Lymphocytic infiltration of pleural mesothelioma and is significance for survival. S Afr Med J 1982, 61:1007–1009.

    PubMed  CAS  Google Scholar 

  77. Haslam PL, Lukoszek A, Merchant JA, Turnerwarwick M: Lymphocyte responses to phytohemagglutinin in patients with asbestosis and pleural mesothelioma. Clin Exper Immunol 1978, 31:178–188.

    CAS  Google Scholar 

  78. Manning LS, Davis MR, Robinson BWS: Asbestos fibers inhibit the in vitro activity of lymphokine-activated killer (Lak) cells from healthy individuals and patients with malignant mesothelioma. Clin Exper Immunol 1991, 83:85–91.

    Article  CAS  Google Scholar 

  79. Boutin C, Nussbaum E, Monnet I, et al.: Intrapleural treatment with recombinant gamma-interferon in early-stage malignant pleural mesothelioma. Cancer 1994, 74:2460–2467. This trial deserves special mention for its demonstration of a 20% response rate with intrapleural interferon gamma, including eight complete responses in 89 patients.

    Article  PubMed  CAS  Google Scholar 

  80. Robinson BWS, Bowman RV, Manning LS, et al.: Interleukin-2 and lymphokine activated killer cells in malignant pleural mesothelioma. Eur Respir Rev 1993, 3:220–222.

    Google Scholar 

  81. Scagliotti G, Shin D, Kindler H, et al.: Phase II study of ALIMTA (pemetrexed disodium, MTA) single agent in patients with malignant pleural mesothelioma [abstract]. Eur J Cancer 2001, 37:20.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smythe, W.R. Current therapy for malignant mesothelioma. Curr Oncol Rep 4, 305–313 (2002). https://doi.org/10.1007/s11912-002-0006-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-002-0006-2

Keywords

Navigation