Pazopanib

Abstract

Posterior reversible encephalopathy syndrome: case report A 64-year-old woman developed posterior reversible encephalopathy syndrome (PRES) during treatment with pazopanib for uterine sarcoma. The woman, who had a history of hypertension, presented with impaired consciousness. In December 2017, she had been diagnosed with uterine leiomyosarcoma. She received radiotherapy, followed by treatment with doxorubicin in February 2018. Due to progression of the disease and metastases, she was initiated on treatment with oral pazopanib 800 mg/day in June 2018. However, 3 days after pazopanib therapy, she presented with impaired consciousness (current presentation). Her Glasgow Coma Scale score was E4V2M5, with conjugate deviation to the right, paralysis of the right limbs and aphasia. Further evaluations revealed the following: BP of 165/109mm Hg, respiratory rate of 22 breaths/min, oxygen saturation of 99%, body temperature of 36.5°C, HR of 114 beats/min and pupils of diameters 2.5 mm/2.5 mm on left/right, respectively. She also showed sinus rhythm on an electrocardiography. A head CT showed low-density area suggestive of an old cerebral infarct in the left occipital lobe, but did not show a new organic lesion. After the CT, while she was being transferred to her room, she developed a tonic clonic seizure. The woman was treated with diazepam, and her convulsion resolved. However, after she returned to her room, the tonic clonic seizure recurred. Status epilepticus was considered. She received diazepam and fosphenytoin. She was transferred to the ICU, intubated and treated with midazolam. She did not receive anti-hypertensive medication, but her BP spontaneously reduced to 154/105mm Hg. Her pazopanib was discontinued. On day 1 of hospitalisation, an MRI showed high intensity area in the white matter of left occipital lobe; the lesion did not show abnormal high intensity on diffusion-weighted imaging. She did not show intracranial haemorrhage, brain metastasis or cerebral infarction. A diagnosis of PRES was suspected based the presentation including findings suggestive of vasogenic brain oedema. Her midazolam was tapered off on the same day. She was initiated on levetiracetam. Her aphasia, conjugate deviation and paralysis had improved by day 2. Her Glasgow Coma Scale score improved to E4VTM6 and she was extubated. Her levetiracetam was continued. Her BP showed a temporary increase to 164/100mm Hg, and nicardipine was initiated. Her BP reduced to 122/64mm Hg, nicardipine was tapered off by day 3 and amlodipine was started. Resolution of the high intensity (noted on day 1) was seen on a brain MRI on day 7, confirming a diagnosis of PRES. Her cerebral oedema had improved and neurological symptoms had resolved without residual symptoms. She was discharged on day 8. Her brain MRI was repeated on day 32, which confirmed resolution of the high intensities in comparison to the MRI on day 7. She was diagnosed with pazopanib-induced PRES. Her history of hypertension and uterine leiomyosarcoma was also considered to be a risk factor in the development of PRES.