Posterior reversible encephalopathy syndrome induced by pazopanib for renal cell carcinoma

Asaithambi, Ganesh; Peters, Brian R.; Hurliman, Elisabeth; Moran, Benedict; Khan, Asrar; Taylor, Robert

doi:10.1111/jcpt.12031

Cited by 26 publications

(18 citation statements)

References 5 publications

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“…In the second case, the patient presented 1 month after starting the drug with headache and nausea. He had a peak systolic blood pressure of 219 mm Hg and MRI brain showed bilateral parieto-occipital oedema 7. In the most recent case, the patient presented with seizures and left arm paresis 8 weeks after starting pazopanib.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, these reported tyrosine kinase inhibitors partially exert their antitumour effect through inhibition of vascular endothelial growth factor receptor (VEGFR) and, in turn, angiogenesis 6. Although the exact mechanism is unclear, vascular endothelial growth factor receptor (VEGFR) inhibition has been theorised to play a prominent role in the development of PRES in these agents because VEGFR inhibition leads to endothelial dysfunction, which, in turn, leads to capillary leakage and cerebral oedema 7. The role of VEGFR inhibition is supported by one report of a patient who developed PRES without a significant change in blood pressure while on bevacizumab, which is a monoclonal antibody that also inhibits VEGFR 8…”

Section: Discussionmentioning

confidence: 99%

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Pazopanib-associated posterior reversible encephalopathy syndrome with intracerebral haemorrhage

Miller-Patterson

Fehnel

2017

BMJ Case Reports

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Pazopanib is a tyrosine kinase receptor antagonist used for renal cell carcinoma and soft tissue sarcoma that inhibits tumour growth and angiogenesis. A common side effect of pazopanib is hypertension. We report a case of a 69-year-old woman with clear cell renal cell carcinoma who developed a large right occipital intracerebral haemorrhage 3 weeks after initiating pazopanib. Although this was initially suspected to be a haemorrhagic metastasis, MRI revealed bi-occipital oedema, supporting a diagnosis of posterior reversible encephalopathy syndrome (PRES). A craniectomy was required. Immunohistochemical stains for renal cell carcinoma antigen, CA IX and PAX8 were negative. This case suggests that PRES and intracerebral haemorrhage may result from pazopanib use and are important complications to consider prior to initiating this agent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pazopanib-associated posterior reversible encephalopathy syndrome with intracerebral haemorrhage

Miller-Patterson

Fehnel

2017

BMJ Case Reports

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“…Hypertension has been described as the cause of RPLS [7], and various case reports have been published about patients developing RPLS under sunitinib, sorafenib and bevacizumab therapy [8, 9, 10, 11, 12, 13, 14, 15]. Only recently two cases of RPLS under treatment with pazopanib have been reported [16, 17]. The history of our patient shows that if hypertension occurs under treatment with one TKI there is a strong possibility that it will occur under another TKI as well.…”

Section: Discussionmentioning

confidence: 99%

Posterior Reversible Leukoencephalopathy Syndrome Associated with Pazopanib

et al. 2013

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A 62-year-old female patient with metastatic renal cell carcinoma under third-line treatment with pazopanib for 8 weeks suddenly developed severe headaches, grand mal seizures and paresis of the left arm in combination with gait instability as well as nausea and vomiting during her vacation abroad. The emergency physician measured systolic blood pressure values over 300 mm Hg and suspected a stroke. The CT imaging without contrast agent in a local hospital did not show any pathologic findings despite bone metastases. The colleagues suspected cerebral metastases or meningeosis carcinomatosa and referred the patient to our department for further diagnostics and treatment planning. An MRI scan ruled out the suspected cerebral metastases or meningeosis carcinomatosa, but showed signs of reversible posterior leukoencephalopathy syndrome (RPLS) in the form of band-like hyperintensities as a sign of cytotoxic edema in the gray and white matter of the left parietal lobe. The patient then reported that similar blood pressure values had been measured shortly after the start of a first-line therapy with sunitinib, so that we discontinued the current treatment with pazopanib. Within 6 days the neurologic symptoms vanished and the patient was discharged. An intermittent hypertension persisted. A follow-up MRI 3 weeks later showed an RPLS-typical cortical infarction in the affected area. RPLS should be considered as the actual reason for neurologic findings in hypertensive patients with known metastatic cancers under tyrosine kinase inhibitor therapy.

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“…Recently, a growing number of case reports have documented the onset of PRES following the use of the anti-VEGF therapies bevacizumab, aflibercept, sorafenib, sunitinib, pazopanib and axitinib [4,5,[18][19][20]. Anti-VEGF therapies, including sorafenib, have been shown to cause vascular side effects, leading to severe cardiac and neurovascular effects associated with PRES.…”

Section: Introductionmentioning

confidence: 99%

“…Anti-VEGF therapies, including sorafenib, have been shown to cause vascular side effects, leading to severe cardiac and neurovascular effects associated with PRES. However, the neurotoxic effects of this class of targeted therapies remain poorly understood [4,[18][19][20]. The pathogenesis of PRES itself remains unclear and controversial, but it appears to be related to disordered cerebrovascular autoregulation and endothelial dysfunction [4-8, 10, 12, 15].…”

Section: Introductionmentioning

confidence: 99%

Posterior Reversible Encephalopathy Syndrome Associated with Sorafenib and Successful Retreatment

Laruelle

Filleul²,

Duprez³

et al. 2016

Urol Int

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Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome characterized by acute hypertension, headache, decreased level of consciousness, visual disturbances and seizures associated with characteristic neuroimaging changes indicative of vasogenic edema of the posterior cerebral white matter. Several medical conditions have been associated with PRES including hypertensive encephalopathy and eclampsia. The use of cytotoxic and immunosuppressant drugs, such as those which target vascular endothelial growth factor (VEGF), have also been implicated. We report here the case of a 71-year-old woman with metastatic clear cell renal carcinoma who developed PRES 3 months after commencing sorafenib. Elevated blood pressure (BP) was recorded, and MRI of the brain) of the brain showed asymmetric areas of increased signal intensity within the supratentorial white matter suggestive of PRES. Clinical and radiological features rapidly improved with BP control and discontinuation of sorafenib. Sorafenib was resumed with no sign of PRES recurrence. The present case report supports the hypothesis that, in selected patients, the re-introduction of anti-VEGF therapies after PRES is feasible.

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Posterior reversible encephalopathy syndrome induced by pazopanib for renal cell carcinoma

Abstract: There are no known reports of the association between PRES and pazopanib. We postulate that pazopanib can disrupt the normal endothelial function of the brain leading to the development of PRES.

Cited by 26 publications

References 5 publications

Pazopanib-associated posterior reversible encephalopathy syndrome with intracerebral haemorrhage

Pazopanib-associated posterior reversible encephalopathy syndrome with intracerebral haemorrhage

Posterior Reversible Leukoencephalopathy Syndrome Associated with Pazopanib

Posterior Reversible Encephalopathy Syndrome Associated with Sorafenib and Successful Retreatment

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