P14.07 Posterior reversible encephalopathy syndrome and new hormone therapy for prostate cancer

Abstract

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a clinical radiographic entity characterized by acute or sub acute neurological symptoms with vasogenic sub cortical edema in parieto-occipital regions. The pathogenesis is not completely understood, however, endothelial dysfunction seems to be a key factor. Enzalutamide is an androgen receptor antagonist approved in the treatment of metastatic castration-resistant prostate cancer. PRES it's only described in enzalutamide post-marketing reports. Material And Methods: clinical data and literature review RESULTS: A 74 years-old man diagnosed with prostate adenocarcinoma Gleason 7, stage II in 2004, was treated with radical prostatectomy. In 2008 he had a biochemical failure and he was submitted to pelvic radio therapy without benefit. He started goserelin 10,8 mg q3m in order to achieve castration levels. In 2011 the patient became castration resistance with adenopathy and bone metastasis. He was submitted to 2 courses of docetaxel 75mg/m2, 10 cycles each, q21d, with clinical benefit. In 2014, he started cabazitaxel 25mg/m2 q21d, suspended after 4 cycles for hematologic toxicity. The patient had a good performance status, so he started in January 2015 enzalutamide 160 mg/day with clinical benefit. 9 months after, he developed reduced visual acuity and imbalance gait with 10 days of evolution. CT revealed a hypodense cortico-subcortical parietal-occipital nonspecific area. MRI showed suggestive images of PRES. Enzalutamide was suspended and LHRH agonist was kept. Response assessment documented disease progression and additional exams weren't performed due the progressive clinical deterioration related with malignant disease. One month after enzalutamide suspension, the patient died due the prostate cancer. This syndrome has an increasingly recognition in the past two decades due the wider use of brain imaging tests. Endothelial dysfunction may be caused by abrupt increase in blood pressure that exceeds the threshold of cerebral pressure or excessive circulating cytokines that cause direct damage in the endothelium. This damage increases vascular permeability and leads to cerebral edema. Endothelial damage may be related with the development of PRES in patients with normal blood pressure and patients submitted to cytotoxic agents. Until March 2016 were reported 8 enzalutamide-induced cases in European Medicines Agency. Despite the name, this entity is not always totally reversible, persisting sequelae in 10-20% of the patients with PRES. Conclusion: PRES is a rare side effect of enzalutamide described in the post-marketing. Other etiologic causes in this patient weren't excluded but our presumptive diagnosis was PRES. This case alerts that we must be vigilant to rare side effects that emerge with the use of new drugs and aren't described in clinical trials.