Skip to main content

Antiangiogenic Therapies for Mesothelioma: What Is the Role in Mesothelioma Treatment?

  • Chapter
  • First Online:
Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma is known for its correlation between angiogenic factors and survival. In this chapter, we focus on the background of this phenomenon and present the available data of studies with antiangiogenic agents. To date, only limited signals have been found that interventions using these agents are of great impact of the disease. It is concluded that single-agent approaches are futile and should be tested in combination with chemotherapy or in a multimodality setting.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182–6.

    Article  CAS  Google Scholar 

  2. Wood S Jr. Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. AMA Arch Pathol. 1958;66(4):550–68.

    PubMed  Google Scholar 

  3. Greenblatt M, Shubi P. Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst. 1968;41(1):111–24.

    CAS  PubMed  Google Scholar 

  4. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358(19):2039–49.

    Article  CAS  Google Scholar 

  5. Ohta Y, Shridhar V, Bright RK, Kalemkerian GP, Du W, Carbone M, et al. VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. Br J Cancer. 1999;81(1):54–61.

    Article  CAS  Google Scholar 

  6. Kumar-Singh S, Vermeulen PB, Weyler J, Segers K, Weyn B, Van Daele A, et al. Evaluation of tumour angiogenesis as a prognostic marker in malignant mesothelioma. J Pathol. 1997;182(2):211–6.

    Article  CAS  Google Scholar 

  7. Edwards JG, Cox G, Andi A, Jones JL, Walker RA, Waller DA, et al. Angiogenesis is an independent prognostic factor in malignant mesothelioma. Br J Cancer. 2001;85(6):863–8.

    Article  CAS  Google Scholar 

  8. Yasumitsu A, Tabata C, Tabata R, Hirayama N, Murakami A, Yamada S, et al. Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma. J Thorac Oncol. 2010;5(4):479–83.

    Article  Google Scholar 

  9. Langerak AW, De Laat PA, Van Der Linden-Van Beurden CA, Delahaye M, Van Der Kwast TH, Hoogsteden HC, et al. Expression of platelet-derived growth factor (PDGF) and PDGF receptors in human malignant mesothelioma in vitro and in vivo. J Pathol. 1996;178(2):151–60.

    Article  CAS  Google Scholar 

  10. Honda M, Kanno T, Fujita Y, Gotoh A, Nakano T, Nishizaki T. Mesothelioma cell proliferation through autocrine activation of PDGF-betabeta receptor. Cell Physiol Biochem. 2012;29(5–6):667–74.

    Article  CAS  Google Scholar 

  11. Schelch K, Hoda MA, Klikovits T, Munzker J, Ghanim B, Wagner C, et al. Fibroblast growth factor receptor inhibition is active against mesothelioma and synergizes with radio- and chemotherapy. Am J Respir Crit Care Med. 2014;190(7):763–72.

    Article  CAS  Google Scholar 

  12. Tsao AS, He D, Saigal B, Liu S, Lee JJ, Bakkannagari S, et al. Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion. Mol Cancer Ther. 2007;6(7):1962–72.

    Article  CAS  Google Scholar 

  13. Khusial PR, Vadla B, Krishnan H, Ramlall TF, Shen Y, Ichikawa H, et al. Src activates Abl to augment Robo1 expression in order to promote tumor cell migration. Oncotarget. 2010;1(3):198–209.

    Article  Google Scholar 

  14. Dubey S, Janne PA, Krug L, Pang H, Wang X, Heinze R, et al. A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307. J Thorac Oncol. 2010;5(10):1655–61.

    Article  Google Scholar 

  15. Papa S, Popat S, Shah R, Prevost AT, Lal R, McLennan B, et al. Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy. J Thorac Oncol. 2013;8(6):783–7.

    Article  CAS  Google Scholar 

  16. Laurie SA, Gupta A, Chu Q, Lee CW, Morzycki W, Feld R, et al. Brief report: a phase II study of sunitinib in malignant pleural mesothelioma. The NCIC Clinical Trials Group. J Thorac Oncol. 2011;6(11):1950–4.

    Article  Google Scholar 

  17. Nowak AK, Millward MJ, Creaney J, Francis RJ, Dick IM, Hasani A, et al. A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma. J Thorac Oncol. 2012;7(9):1449–56.

    Article  CAS  Google Scholar 

  18. Camidge DR, Blais N, Jonker DJ, Soulieres D, Doebele RC, Ruiz-Garcia A, et al. Sunitinib combined with pemetrexed and cisplatin: results of a phase I dose-escalation and pharmacokinetic study in patients with advanced solid malignancies, with an expanded cohort in non-small cell lung cancer and mesothelioma. Cancer Chemother Pharmacol. 2013;71(2):307–19.

    Article  CAS  Google Scholar 

  19. Garland LL, Chansky K, Wozniak AJ, Tsao AS, Gadgeel SM, Verschraegen CF, et al. Phase II study of cediranib in patients with malignant pleural mesothelioma: SWOG S0509. J Thorac Oncol. 2011;6(11):1938–45.

    Article  Google Scholar 

  20. Campbell NP, Kunnavakkam R, Leighl N, Vincent MD, Gandara DR, Koczywas M, et al. Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium. Lung Cancer. 2012;78(1):76–80.

    Article  Google Scholar 

  21. Tsao AS, Miao J, Wistuba II, Vogelzang NJ, Heymach JV, Fossella FV, et al. Phase II trial of Cediranib in combination with Cisplatin and Pemetrexed in chemotherapy-naive patients with unresectable malignant pleural mesothelioma (SWOG S0905). J Clin Oncol. 2019;37(28):2537–47.

    Article  CAS  Google Scholar 

  22. Jahan T, Gu L, Kratzke R, Dudek A, Otterson GA, Wang X, et al. Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107). Lung Cancer. 2012;76(3):393–6.

    Article  Google Scholar 

  23. Laurie SA, Hao D, Leighl NB, Goffin J, Khomani A, Gupta A, et al. A phase II trial of dovitinib in previously-treated advanced pleural mesothelioma: the Ontario Clinical Oncology Group. Lung Cancer. 2017;104:65–9.

    Article  Google Scholar 

  24. Kindler HL, Karrison TG, Gandara DR, Lu C, Krug LM, Stevenson JP, et al. 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(20):2509–15.

    Article  CAS  Google Scholar 

  25. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010;21(9):1804–9.

    Article  CAS  Google Scholar 

  26. Jubb AM, Hurwitz HI, Bai W, Holmgren EB, Tobin P, Guerrero AS, et al. Impact of vascular endothelial growth factor-a expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol. 2006;24(2):217–27.

    Article  CAS  Google Scholar 

  27. Ceresoli GL, Zucali PA, Mencoboni M, Botta M, Grossi F, Cortinovis D, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer. 2013;109(3):552–8.

    Article  CAS  Google Scholar 

  28. Dowell JE, Dunphy FR, Taub RN, Gerber DE, Ngov L, Yan J, et al. A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma. Lung Cancer. 2012;77(3):567–71.

    Article  Google Scholar 

  29. Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10026):1405–14.

    Article  CAS  Google Scholar 

  30. Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010;28(22):3617–22.

    Article  CAS  Google Scholar 

  31. Shaked Y, Henke E, Roodhart JM, Mancuso P, Langenberg MH, Colleoni M, et al. Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. Cancer Cell. 2008;14(3):263–73.

    Article  CAS  Google Scholar 

  32. Grosso F, Steele N, Novello S, Nowak AK, Popat S, Greillier L, et al. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: phase II results from the randomized, placebo-controlled LUME-meso trial. J Clin Oncol. 2017;35(31):3591–600.

    Article  CAS  Google Scholar 

  33. Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, et al. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019;7(7):569–80.

    Article  CAS  Google Scholar 

  34. Buikhuisen WA, Scharpfenecker M, Griffioen AW, Korse CM, van Tinteren H, Baas P. A randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma: a single-center trial combining clinical and translational outcomes. J Thorac Oncol. 2016;11(5):758–68.

    Article  Google Scholar 

  35. Baas P, Boogerd W, Dalesio O, Haringhuizen A, Custers F, van Zandwijk N. Thalidomide in patients with malignant pleural mesothelioma. Lung Cancer. 2005;48(2):291–6.

    Article  Google Scholar 

  36. Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, et al. 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(6):543–51.

    Article  CAS  Google Scholar 

  37. Kaur S, Chang T, Singh SP, Lim L, Mannan P, Garfield SH, et al. CD47 signaling regulates the immunosuppressive activity of VEGF in T cells. J Immunol. 2014;193(8):3914–24.

    Article  CAS  Google Scholar 

  38. Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288–301.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wieneke Buikhuisen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Buikhuisen, W., Baas, P. (2021). Antiangiogenic Therapies for Mesothelioma: What Is the Role in Mesothelioma Treatment?. In: Nakano, T., Kijima, T. (eds) Malignant Pleural Mesothelioma. Respiratory Disease Series: Diagnostic Tools and Disease Managements. Springer, Singapore. https://doi.org/10.1007/978-981-15-9158-7_21

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-9158-7_21

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-9157-0

  • Online ISBN: 978-981-15-9158-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics