Atypical reversible posterior leukoencephalopathy syndrome (RPLS) induced by cediranib in a patient with metastatic rectal cancer

Invest New Drugs. 2014 Oct;32(5):1036-45. doi: 10.1007/s10637-014-0113-6. Epub 2014 May 23.

Abstract

Background: Reversible posterior leukoenecphalopathy syndrome (RPLS) is a rare clinicoradiologic syndrome characterized by neurologic symptoms such as seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of posterior white matter seen on neuroimaging. It has been reported in association with many anti-angiogenic therapies, including bevacizumab, sunitinib, sorafenib, pazopanib and regorafenib. Cediranib is a potent, orally available small molecule tyrosine kinase inhibitor with anti-angiogenic activity, which has been shown to have activity against various solid tumors.

Case report: We present a case of a 65 year old male with metastatic adenocarcinoma of the rectum who received cediranib as part of a phase I clinical trial. He developed confusion and fluctuations in his level of consciousness. MRI of the brain revealed diffuse low level T2 signal abnormality in the cerebral peduncles, pons, and medulla and patchy T2 signal in both thalami, consistent with RPLS. With conservative management, including tight blood pressure control, his symptoms improved and MRI findings resolved.

Conclusion: RPLS is a rare, but serious, clinicoradiologic syndrome which has been described as an adverse effect of many anti-angiogenic agents and should also be considered in patients on cediranib who present with neurologic symptoms along with vasogenic edema seen on MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure should be aggressively controlled.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Humans
  • Male
  • Posterior Leukoencephalopathy Syndrome / chemically induced*
  • Protein Kinase Inhibitors / adverse effects*
  • Quinazolines / adverse effects*
  • Rectal Neoplasms / drug therapy

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • cediranib