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Reversible Posterior Leukoencephalopathy Syndrome Induced by Sunitinib

University Hospital of Salamanca, Salamanca, Spain

To the Editor:

We would like to report the occurrence of reversible posterior leukoencephalopathy that we believe is directly attributable to sunitinib malate (Sutent; Pfizer Pharmaceuticals Group, New York, NY), a receptor tyrosine kinase inhibitor with antiangiogenic activity that is approved for the treatment of advanced renal cell carcinoma.

A 70-year-old woman diagnosed with renal cell carcinoma and bone metastasis was first treated with palliative nefrectomy and interferon plus vinblastine. Afterwards, she was enrolled in a phase II clinical trial with sunitinib malate (50 mg daily for 4 weeks every 6 weeks). Two weeks after starting the treatment, she was admitted to the hospital because of partial seizures affecting her left superior extremity, headache, and vision loss in the previous 2 days. The physical examination was normal except for cortical blindness and hypertension (170/100 mmHg). Blood tests, including coagulation study and gasometry, were unremarkable. Computed tomography of the brain showed symmetric subcortical hypodense lesions in the occipital lobes, consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Magnetic resonance imaging was requested to rule out brain micrometastasis and it confirmed the findings of RPLS: symmetric hyperintense T2 signal involving bilateral occipital and parietal lobes in the subcortical distribution (Fig 1). Sunitinib administration was withheld and the patient was treated with anticonvulsants and antihypertensives. She recovered completely, was discharged in a few days and had a normal brain computed tomography performed 1 month later.

View larger version (61K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. Magnetic resonance imaging scan of the brain of a patient with leukoencephalopathy. Symmetric hyperintense T2 signal involving occipital and parietal lobes.

Sunitinib has a dual activity: extracellular action against vascular endothelial growth factor receptor (antiangiogenic) and intracellular action against tyrosine kinase domains, which can produce hypertension. In our case, the set of symptoms could be caused through both mechanisms.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Hinchey J, Chaves C, Appignani B, et al: A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334:494-500, 1996[Abstract/Free Full Text]

2. Saito B, Nakamaki T, Nakashima H, et al: Reversible posterior leukoencephalopathy syndrome after repeat intermediate-dose cytarabine chemotherapy in a patient with acute myeloid leukemia. Am J Hematol 82:304-306, 2007[CrossRef][Medline]

3. Ozcan C, Wong S, Hari P: Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 354:981, 2006

4. Glusker P, Recht L, Lane B: Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 354:980-981, 2006[Free Full Text]

5. Govindarajan R, Adusumilli J, Baxter DL, et al: Reversible posterior leukoencephalopathy syndrome induced by RAF kinase inhibitor BAY 43-9006. J Clin Oncol 24:e48, 2006[Free Full Text]

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