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Systemic Therapies in Malignant Pleural Mesothelioma

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Principles and Practice of Radiotherapy Techniques in Thoracic Malignancies

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Abstract

Malignant pleural mesothelioma (MPM) arises from pleura surface and characterized by aggressive clinical course. In patients with MPM chest pain, cough, and dyspnea are the most common presenting symptoms at admission. Degrees of symptoms are gradually increased. After radiological staging of the disease, the candidate patients for the surgery are determined. The extent of disease and clinical status of patient should be evaluated by a multidisciplinary team. At the time of diagnosis, 20 % of the patients have resectable disease. Although it was not proven in phase III trials, the patients candidate for surgery are treated with combined systemic chemotherapy and radiotherapy. The aim of the surgery is to achieve macroscopic complete resection. The medically operable patients with stage I-III disease can receive chemotherapy before or after chemotherapy.

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References

  1. Alley EW, Molife L, Santoro A et al. Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: preliminary results from KEYNOTE-028 (abstract CT103). American Association of Cancer Research 2015 meeting.

    Google Scholar 

  2. Altomare DA, You H, Xiao GH, Ramos-Nino ME, Skele KL, de Rienzo A, Jhanwar SC, Mossman BT, Kane AB, Testa JR. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene. 2005;24:6080–9.

    Article  CAS  PubMed  Google Scholar 

  3. Baas P, Ardizzoni A, Grossi F, Nackaerts K, Numico G, van Marck E, van de Vijver M, Monetti F, Smid-Geirnaerdt MJ, van Zandwijk N, Debruyne C, Legrand C, Giaccone G. The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: an EORTC phase II study (08992). Eur J Cancer. 2003;39:353–7.

    Article  CAS  PubMed  Google Scholar 

  4. Baas P, Boogerd W, Dalesio O, Haringhuizen A, Custers F, van Zandwijk N. Thalidomide in patients with malignant pleural mesothelioma. Lung Cancer. 2005;48:291–6.

    Article  PubMed  Google Scholar 

  5. Berghmans T, Paesmans M, Lalami Y, Louviaux I, Luce S, Mascaux C, Meert AP, Sculier JP. Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis. Lung Cancer. 2002;38:111–21.

    Article  CAS  PubMed  Google Scholar 

  6. Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, Pavlakis N, Nowak AK, Custers FL, Schouwink JH, Gans SJ, Groen HJ, Strankinga WF, Baas P. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2013;14:543–51.

    Article  CAS  PubMed  Google Scholar 

  7. Calabro L, Morra A, Fonsatti E, Cutaia O, Amato G, Giannarelli D, di Giacomo AM, Danielli R, Altomonte M, Mutti L, Maio M. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013;14:1104–11.

    Article  CAS  PubMed  Google Scholar 

  8. Castagneto B, Zai S, Dongiovanni D, Muzio A, Bretti S, Numico G, Botta M, Sinaccio G. Cisplatin and gemcitabine in malignant pleural mesothelioma: a phase II study. Am J Clin Oncol. 2005;28:223–6.

    Article  CAS  PubMed  Google Scholar 

  9. Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ, Santoro A. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006;24:1443–8.

    Article  CAS  PubMed  Google Scholar 

  10. Ellis P, Davies AM, Evans WK, Haynes AE, Lloyd NS. The use of chemotherapy in patients with advanced malignant pleural mesothelioma: a systematic review and practice guideline. J Thorac Oncol. 2006;1:591–601.

    Article  PubMed  Google Scholar 

  11. Janne PA, Simon GR, Langer CJ, Taub RN, Dowlati A, Fidias P, Monberg M, Obasaju C, Kindler H. Phase II trial of pemetrexed and gemcitabine in chemotherapy-naive malignant pleural mesothelioma. J Clin Oncol. 2008;26:1465–71.

    Article  CAS  PubMed  Google Scholar 

  12. Janne PA, Wozniak AJ, Belani CP, Keohan ML, Ross HJ, Polikoff JA, Mintzer DM, Ye Z, Monberg MJ, Obasaju CK. Pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program. J Thorac Oncol. 2006;1:506–12.

    Article  PubMed  Google Scholar 

  13. Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, Blatter J, Adachi S, Hanauske A, Manegold C. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008;26:1698–704.

    Article  CAS  PubMed  Google Scholar 

  14. Kindler HL, Karrison TG, Gandara DR, Lu C, Krug LM, Stevenson JP, Janne PA, Quinn DI, Koczywas MN, Brahmer JR, Albain KS, Taber DA, Armato 3rd SG, Vogelzang NJ, Chen HX, Stadler WM, Vokes EE. Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. J Clin Oncol. 2012;30:2509–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, Ohman R, Plummer R, Eberhardt WE, Fukuoka K, Gaafar RM, Lafitte JJ, Hillerdal G, Chu Q, Buikhuisen WA, Lubiniecki GM, Sun X, Smith M, Baas P. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015;16:447–56.

    Article  CAS  PubMed  Google Scholar 

  16. Krug LM, Pass HI, Rusch VW, Kindler HL, Sugarbaker DJ, Rosenzweig KE, Flores R, Friedberg JS, Pisters K, Monberg M, Obasaju CK, Vogelzang NJ. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27:3007–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Magri MD, Veronesi A, Foladore S, de Giovanni D, Serra C, Crismancich F, Tuveri G, Nicotra M, Tommasi M, Morassut S, et al. Epirubicin in the treatment of malignant mesothelioma: a phase II cooperative study. The North-Eastern Italian Oncology Group (GOCCNE) – Mesothelioma Committee. Tumori. 1991;77:49–51.

    CAS  PubMed  Google Scholar 

  18. Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005;16:923–7.

    Article  CAS  PubMed  Google Scholar 

  19. Martinez-Iglesias O, Ruiz-Llorente L, Sanchez-Martinez R, Garcia L, Zambrano A, Aranda A. Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer. Clin Transl Oncol. 2008;10:395–8.

    Article  CAS  PubMed  Google Scholar 

  20. Mathy A, Baas P, Dalesio O, van Zandwijk N. Limited efficacy of imatinib mesylate in malignant mesothelioma: a phase II trial. Lung Cancer. 2005;50:83–6.

    Article  PubMed  Google Scholar 

  21. Ou SH, Moon J, Garland LL, Mack PC, Testa JR, Tsao AS, Wozniak AJ, Gandara DR. SWOG S0722: phase II study of mTOR inhibitor everolimus (RAD001) in advanced malignant pleural mesothelioma (MPM). J Thorac Oncol. 2015;10:387–91.

    Article  CAS  PubMed  Google Scholar 

  22. Porta C, Mutti L, Tassi G. Negative results of an Italian Group for Mesothelioma (G.I.Me.) pilot study of single-agent imatinib mesylate in malignant pleural mesothelioma. Cancer Chemother Pharmacol. 2007;59:149–50.

    Article  PubMed  Google Scholar 

  23. Righi L, Papotti MG, Ceppi P, Bille A, Bacillo E, Molinaro L, Ruffini E, Scagliotti GV, Selvaggi G. Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy. J Clin Oncol. 2010;28:1534–9.

    Article  CAS  PubMed  Google Scholar 

  24. Ryan CW, Herndon J, Vogelzang NJ. A review of chemotherapy trials for malignant mesothelioma. Chest. 1998;113:66S–73.

    Article  CAS  PubMed  Google Scholar 

  25. Skubitz KM. Phase II trial of pegylated-liposomal doxorubicin (Doxil) in mesothelioma. Cancer Invest. 2002;20:693–9.

    Article  CAS  PubMed  Google Scholar 

  26. 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;65:956–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Steele JP, Shamash J, Evans MT, Gower NH, Tischkowitz MD, Rudd RM. Phase II study of vinorelbine in patients with malignant pleural mesothelioma. J Clin Oncol. 2000;18:3912–7.

    CAS  PubMed  Google Scholar 

  28. Sterman DH, Kaiser LR, Albelda SM. Advances in the treatment of malignant pleural mesothelioma. Chest. 1999;116:504–20.

    Article  CAS  PubMed  Google Scholar 

  29. Symanowski JT, Rusthoven J, Nguyen B, et al. Multiple regression analysis of prognostic variables for survival from the phase III study of pemetrexed plus cisplatin vs. cisplatin in malignant pleural mesothelioma. Proc Am Soc Clin Oncol. 2003;22:647a.

    Google Scholar 

  30. Toyokawa G, Takenoyama M, Hirai F, Toyozawa R, Inamasu E, Kojo M, Morodomi Y, Shiraishi Y, Takenaka T, Yamaguchi M, Shimokawa M, Seto T, Ichinose Y. Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy. Int J Clin Oncol. 2014;19:601–6.

    Article  CAS  PubMed  Google Scholar 

  31. van Haarst JM, Baas P, Manegold C, Schouwink JH, Burgers JA, de Bruin HG, Mooi WJ, van Klaveren RJ, de Jonge MJ, van Meerbeeck JP. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002;86:342–5.

    Article  PubMed  PubMed Central  Google Scholar 

  32. van Meerbeeck JP, Gaafar R, Manegold C, van Klaveren RJ, van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005;23:6881–9.

    Article  PubMed  Google Scholar 

  33. Vogelzang NJ. Chemotherapy for malignant pleural mesothelioma. Lancet. 2008;371:1640–2.

    Article  PubMed  Google Scholar 

  34. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636–44.

    Article  CAS  PubMed  Google Scholar 

  35. Weder W, Stahel RA, Bernhard J, Bodis S, Vogt P, Ballabeni P, Lardinois D, Betticher D, Schmid R, Stupp R, Ris HB, Jermann M, Mingrone W, Roth AD, Spiliopoulos A. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Ann Oncol. 2007;18:1196–202.

    Article  CAS  PubMed  Google Scholar 

  36. Zalcman G, Mazières J, Margery J et al. Bevacizumab 15mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in Malignant Pleural Mesothelioma (MPM): results of the IFCT-GFPC-0701 MAPS randomized phase 3 trial. J Clin Oncol. 2015;33(suppl; abstr 7500).

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Ankara Numune Education & Research Hospital, Sihhiye, 06410, Ankara, Turkey

    Ozan Yazici

  2. Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Sercan Aksoy MD

Authors
  1. Ozan Yazici
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  2. Sercan Aksoy MD
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Correspondence to Sercan Aksoy MD .

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Editors and Affiliations

  1. Department of Radiation Oncology, Hacettepe University, Faculty of Med., Ankara, Turkey

    Gokhan Ozyigit

  2. Department of Radiation Oncology, Koc University, Faculty of Medicine, Istanbul, Turkey

    Ugur Selek

  3. Department of Radiation Oncology, Baskent University School of Medicine, Adana, Turkey

    Erkan Topkan

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Yazici, O., Aksoy, S. (2016). Systemic Therapies in Malignant Pleural Mesothelioma. In: Ozyigit, G., Selek, U., Topkan, E. (eds) Principles and Practice of Radiotherapy Techniques in Thoracic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-28761-4_22

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  • DOI: https://doi.org/10.1007/978-3-319-28761-4_22

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  • Online ISBN: 978-3-319-28761-4

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