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Targeted Oncology

, Volume 6, Issue 4, pp 253–258 | Cite as

Posterior reversible encephalopathy syndrome induced by anti-VEGF agents

  • Camille Tlemsani
  • Olivier Mir
  • Pascaline Boudou-Rouquette
  • Olivier Huillard
  • Karin Maley
  • Stanislas Ropert
  • Romain Coriat
  • François Goldwasser
Day-to-Day Practice

Abstract

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agents. We carried out a comprehensive review of reports documenting the occurrence of PRES in patients receiving anti-VEGF agents. Twenty-six patients are described with a majority of females (73.1%). Almost a third of patients had a past history of hypertension. The most common symptoms included headache, visual disturbance and seizure. A vast majority of patients had hypertension at the diagnosis of PRES, and proteinuria was detectable each time it was investigated. Neurological outcome was favorable in all cases with a symptomatic treatment including blood pressure control. The risk of PRES is increased when blood pressure is poorly controlled and when proteinuria is detectable. The clinical course appears favorable with a symptomatic treatment. PRES is a potentially severe but manageable toxicity of anti-VEGF agents.

Keywords

Reversible posterior leukoencephalopathy syndrome Angiogenesis inhibitors VEGF-A Cancer Outcomes 

Notes

Conflicts of interest statement

Dr. Mir has acted as paid consultant for Roche. Prof. Goldwasser has acted as paid consultant for Pfizer and Bayer. The other authors have no conflict of interest to declare.

References

  1. 1.
    Feske SK (2011) Posterior reversible encephalopathy syndrome: a review. Semin Neurol 31(2):202–215PubMedCrossRefGoogle Scholar
  2. 2.
    Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A et al (1996) A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334(8):494–500PubMedCrossRefGoogle Scholar
  3. 3.
    Hinchey JA (2008) Reversible posterior leukoencephalopathy syndrome: what have we learned in the last 10 years? Arch Neurol 65(2):175–176PubMedCrossRefGoogle Scholar
  4. 4.
    Glusker P, Recht L, Lane B (2006) Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 354(9):980–982, discussion 980–982PubMedCrossRefGoogle Scholar
  5. 5.
    Govindarajan R, Adusumilli J, Baxter DL, El-Khoueiry A, Harik SI (2006) Reversible posterior leukoencephalopathy syndrome induced by RAF kinase inhibitor BAY 43–9006. J Clin Oncol 24(28):e48PubMedCrossRefGoogle Scholar
  6. 6.
    Kapiteijn E, Brand A, Kroep J, Gelderblom H (2007) Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukencephalopathy syndrome. Ann Oncol 18(10):1745–1747PubMedCrossRefGoogle Scholar
  7. 7.
    Leighl NB, Raez LE, Besse B, Rosen PJ, Barlesi F, Massarelli E et al (2010) A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum- and erlotinib-resistant adenocarcinoma of the lung. J Thorac Oncol 5(7):1054–1059PubMedGoogle Scholar
  8. 8.
    Mir O, Ropert S, Alexandre J, Goldwasser F (2009) Hypertension as a surrogate marker for the activity of anti-VEGF agents. Ann Oncol 20(5):967–970PubMedCrossRefGoogle Scholar
  9. 9.
    Mir O, Coriat R, Ropert S, Cabanes L, Blanchet B, Camps S et al (2010) Treatment of bevacizumab-induced hypertension by amlodipine. Invest New Drugs. doi: 10.1007/s10637-010-9549-5
  10. 10.
    Scappaticci FA, Skillings JR, Holden SN, Gerber HP, Miller K, Kabbinavar F et al (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99(16):1232–1239PubMedCrossRefGoogle Scholar
  11. 11.
    Dogan E, Aksoy S, Arslan C, Dede DS, Altundag K (2009) Probable sorafenib-induced reversible encephalopathy in a patient with hepatocellular carcinoma. Med Oncol 27(4):1436–1437CrossRefGoogle Scholar
  12. 12.
    Rini BI, Garcia JA, Cooney MM, Elson P, Tyler A, Beatty K et al (2009) A phase I study of sunitinib plus bevacizumab in advanced solid tumors. Clin Cancer Res 15(19):6277–6283PubMedCrossRefGoogle Scholar
  13. 13.
    Artunay O, Yuzbasioglu E, Rasier R, Sengul A, Bahcecioglu H (2010) Posterior reversible encephalopathy syndrome after intravitreal bevacizumab injection in patient with choroidal neovascular membrane secondary to age-related maculopathy. J Ocul Pharmacol Ther 26(3):301–303PubMedCrossRefGoogle Scholar
  14. 14.
    Burki F, Badie K, Bartoli P, Bernard P, Montastruc JL, Bagheri H (2008) Reversible posterior leukoencephalopathy syndrome associated with bevacizumab/doxorubicin regimen. Br J Clin Pharmacol 65(5):793–794PubMedCrossRefGoogle Scholar
  15. 15.
    Chang Y, Mbeo G, Littman SJ (2011) Reversible posterior leukoencephalopathy syndrome associated with concurrent bevacizumab, gemcitabine, and oxaliplatin for cholangiocarcinoma. J Gastrointest Cancer. doi: 10.1007/s12029-011-9279-8
  16. 16.
    Chen A, Agarwal N (2009) Reversible posterior leucoencephalopathy syndrome associated with sunitinib. Intern Med J 39(5):341–342PubMedCrossRefGoogle Scholar
  17. 17.
    Cumurciuc R, Martinez-Almoyna L, Henry C, Husson H, de Broucker T (2008) Posterior reversible encephalopathy syndrome during sunitinib therapy. Rev Neurol (Paris) 164(6–7):605–607CrossRefGoogle Scholar
  18. 18.
    dos Reis Simões da Silva FM, Burgos Pêgo PM, Henriques Vendrell MC, de Azevedo Batalha Ferreira dos Santos Farias MJ, Ribeiro Timóteo AC, Martins da Costa MC, Monteiro Barbosa Moreira Cravo IM, Ribeiro Gomes FM (2011) Posterior Reversible Encephalopathy Syndrome and Anti-Angiogenic Agents: A Case Report. Neuro-ophtalmology 35(1):32–37Google Scholar
  19. 19.
    El Maalouf G, Mitry E, Lacout A, Lievre A, Rougier P (2008) Isolated brainstem involvement in posterior reversible leukoencephalopathy induced by bevacizumab. J Neurol 255(2):295–296CrossRefGoogle Scholar
  20. 20.
    Feldman DR, Baum MS, Ginsberg MS, Hassoun H, Flombaum CD, Velasco S et al (2009) Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 27(9):1432–1439PubMedCrossRefGoogle Scholar
  21. 21.
    Koopman M, Muller EW, Punt CJ (2008) Reversible posterior leukoencephalopathy syndrome caused by bevacizumab: report of a case. Dis Colon Rectum 51(9):1425–1426PubMedCrossRefGoogle Scholar
  22. 22.
    Lau PC, Paunipagar B (2011) Posterior reversible encephalopathy syndrome with bevacizumab. Hong Kong Med J 17(1):80–81PubMedGoogle Scholar
  23. 23.
    Martin G, Bellido L, Cruz JJ (2007) Reversible posterior leukoencephalopathy syndrome induced by sunitinib. J Clin Oncol 25(23):3559PubMedCrossRefGoogle Scholar
  24. 24.
    Ozcan C, Wong SJ, Hari P (2006) Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 354(9):980–982, discussion 980–982PubMedCrossRefGoogle Scholar
  25. 25.
    Padhy BM, Shanmugam SP, Gupta YK, Goyal A (2011) Reversible posterior leucoencephalopathy syndrome in an elderly male on sunitinib therapy. Br J Clin Pharmacol 71(5):777–779PubMedCrossRefGoogle Scholar
  26. 26.
    Peter S, Hausmann N, Schuster A, Boehm HF (2008) Reversible posterior leukoencephalopathy syndrome and intravenous bevacizumab. Clin Experiment Ophthalmol 36(1):94–96PubMedCrossRefGoogle Scholar
  27. 27.
    van der Veldt AA, van den Eertwegh AJ, Hoekman K, Barkhof F, Boven E (2007) Reversible cognitive disorders after sunitinib for advanced renal cell cancer in patients with preexisting arteriosclerotic leukoencephalopathy. Ann Oncol 18(10):1747–1750PubMedCrossRefGoogle Scholar
  28. 28.
    Medioni J, Cojocarasu O, Banu E, Cassar-Queudeville A, Halimi P, Oudard S (2007) Reversible encephalopathy syndrome secondary to sunitinib for metastatic renal cell carcinoma patient. Targ Oncol 2(3):193–195CrossRefGoogle Scholar
  29. 29.
    Lou E, Turner S, Sumrall A, Reardon DA, Desjardins A, Peters KB et al (2011) Bevacizumab-induced reversible posterior leukoencephalopathy syndrome and successful retreatment in a patient with glioblastoma. J Clin Oncol. doi: 10.1200/JCO.2011.36.1865
  30. 30.
    Seet RC, Rabinstein AA (2011) Clinical features and outcomes of posterior reversible encephalopathy syndrome following bevacizumab treatment. QJM. doi: 10.1093/qjmed/hcr139
  31. 31.
    Pinedo DM, Shah-Khan F, Shah PC (2007) Reversible posterior leukoencephalopathy syndrome associated with oxaliplatin. J Clin Oncol 25(33):5320–5321PubMedCrossRefGoogle Scholar
  32. 32.
    Paker AM, Chi L, Ruiz MC, Loghin ME (2011) Posterior reversible encephalopathy syndrome in patients with cancer. J Clin Oncol 29(suppl):2561Google Scholar
  33. 33.
    Plouet J, Schilling J, Gospodarowicz D (1989) Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8(12):3801–3806PubMedGoogle Scholar
  34. 34.
    Izzedine H, Ederhy S, Goldwasser F, Soria JC, Milano G, Cohen A et al (2009) Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 20(5):807–815PubMedCrossRefGoogle Scholar
  35. 35.
    Tsatsaris V, Goffin F, Munaut C, Brichant JF, Pignon MR, Noel A et al (2003) Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab 88(11):5555–5563PubMedCrossRefGoogle Scholar
  36. 36.
    Patel TV, Morgan JA, Demetri GD, George S, Maki RG, Quigley M et al (2008) A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. J Natl Cancer Inst 100(4):282–284PubMedCrossRefGoogle Scholar
  37. 37.
    Wagner SJ, Acquah LA, Lindell EP, Craici IM, Wingo MT, Rose CH et al (2011) Posterior reversible encephalopathy syndrome and eclampsia: pressing the case for more aggressive blood pressure control. Mayo Clin Proc 86(9):851–856PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Camille Tlemsani
    • 1
  • Olivier Mir
    • 1
  • Pascaline Boudou-Rouquette
    • 1
  • Olivier Huillard
    • 1
  • Karin Maley
    • 1
  • Stanislas Ropert
    • 1
  • Romain Coriat
    • 1
  • François Goldwasser
    • 1
  1. 1.CERIA (Centre for Research on Angiogenesis Inhibitors), Department of Medical Oncology, Cochin Teaching Hospital, AP-HPUniversité Paris DescartesParisFrance

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