Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukencephalopathy syndrome

Abstract

A 54-year-old female with suboptimally controlled hypertension (RR 150/90) and an imatinib-resistant gastrointestinal stromal cell tumor, had been on treatment with sunitinib malate (Sutent, previously known as SU011248; Pfizer, NY), a vascular endothelial growth factor receptor (VEGFR)/c-kit/platelet-derived growth factor receptor (PDGFR)/Flt3 tyrosine kinase inhibitor. The drug was given orally daily 50 mg for a 4-week-on, 2-week-off schedule since November 2005. During the 4-week-on cycles, thrombocytopenia was present, but the platelet counts restored to normal values in the 2-week-off schedule (Figure 1). On treatment with sunitinib, 20% regression of the tumor was seen. On 22 June 2006, in her last week of her 6th 4-week-on cycle, she experienced loss of vision and epileptical insults. Her blood pressure was 210/110 mmHg, papilledema was absent. Significant laboratory findings included a hemoglobin of 7.5 mmol/l, a platelet count of 26 × 10⁹/l, a serum creatinine of 220 μmol/l and a lactate dehydrogenase (LD) of 6505 U/l. Peripheral smear showed 18% schistocytes. D-dimers were increased (>5000 ng/ml), PT 12.7 s, INR 1.1, APTT 24 s, fibrinogen 4.3 g/l and ADAMTS13 (A Disintegrin And Metalloprotease domain, with ThromboSpondin type 1 motif 13) activity measured on day 2 was 40% (normal value 30%–200%). Magnetic resonance imaging (MRI) of the brain showed features of posterior leukencephalopathy with occipital and parietal high-intensity lesions on a T2-weighed scan (Figure 2).