Investigational New Drugs

, Volume 30, Issue 4, pp 1766–1767 | Cite as

Reversible posterior leukoencephalopathy syndrome and trastuzumab

  • Hiroyasu Kaneda
  • Isamu Okamoto
  • Taroh Satoh
  • Kazuhiko Nakagawa


Reversible posterior leukoencephalopathy syndrome (RPLS) is a serious condition that manifests as headache, convulsions, visual disturbance, and a characteristic magnetic resonance image (MRI) of the brain. We now describe a case of RPLS that was likely attributable to trastuzumab, a monoclonal antibody against human epidermal growth factor receptor-2 (HER2). Accumulating evidence has shown that molecular targeted agents, especially those with antiangiogenic activity cause significant hypertension which can lead to development of RPLS. Trastuzumab is also shown to inhibit tumor angiogenesis by decreasing the production of VEGF and activating antiangiogenic factors. In a clinical trial of trastuzumab, adverse effects of trastuzumab include hypertension, even though it is low incidence (∼10%). Although RPLS is potently reversible, it may result in an irreversible brain damage without prompt appropriate treatment. Given the increasing use of trastuzumab in patients with breast cancer, gastric cancer, or other solid tumors, physicians should be aware of this syndrome associated with acute hypertension during trastuzumab treatment.


Reversible posterior leukoencephalopathy syndrome Trastuzumab Gastric cancer Hypertension 


Conflict of interest

The authors declare no conflicts of interest.


  1. 1.
    Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR (1996) A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334:494–500CrossRefPubMedGoogle Scholar
  2. 2.
    Glusker P, Recht L, Lane B (2006) Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 354:980–982, discussion 980–982CrossRefPubMedGoogle Scholar
  3. 3.
    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:e48CrossRefPubMedGoogle Scholar
  4. 4.
    Martin G, Bellido L, Cruz JJ (2007) Reversible posterior leukoencephalopathy syndrome induced by sunitinib. J Clin Oncol 25:3559CrossRefPubMedGoogle Scholar
  5. 5.
    Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK (2002) Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 416:279–280CrossRefPubMedGoogle Scholar
  6. 6.
    Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS (1997) Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 151:1523–1530PubMedGoogle Scholar
  7. 7.
    Wen XF, Yang G, Mao W, Thornton A, Liu J, Bast RC Jr, Le XF (2006) HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy. Oncogene 25:6986–6996CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Hiroyasu Kaneda
    • 1
  • Isamu Okamoto
    • 1
  • Taroh Satoh
    • 1
  • Kazuhiko Nakagawa
    • 1
  1. 1.Department of Medical OncologyKinki University Faculty of MedicineOsakaJapan

Personalised recommendations