Cerebrovascular Ischemic Events in Patients With Advanced Renal Cell Carcinoma Treated With Anti-Angiogenic Tyrosine Kinase Inhibitors: A Report on Two Cases With Different Outcomes

Abstract

Small-molecule tyrosine kinase inhibitors (TKIs), targeting tumor angiogenesis, have revolutionized the treatment of advanced renal cell carcinoma (RCC) over the last decade. Their rationale is that most clear cell RCCs have alterations in the Von Hippel-Lindau (VHL) gene pathway that leads to over-expression of pro-angiogenic factors such as vascular endothelial growth factor and platelet-derived growth factor that drive tumor growth and dissemination. The toxicity profile of these therapies, whilst generally mild and manageable, is quite distinct from that of conventional cytotoxic chemotherapy and immunotherapy. Arterial thrombotic events have been reported with pazopanib and axitinib (1-2% incidence) and patients with recent vascular events have been excluded from phase III trials of these drugs in RCC. We report two cases of cerebral infarction likely related to these treatments in female patients without any history of macrovascular disease or any conventional risk factors such as hyperlipidemia, hypertension or diabetes mellitus. Treatment-related arterial thromboembolism may develop rapidly and unpredictably in these patients and consideration should be given to aggressively monitoring and modifying any pre-existing vascular risk factors. Older patients with risk factors for vascular disease or with a prior history of such events must have an informed discussion regarding the risks and benefits of treatment. It remains to be seen whether prophylactic anti-platelet therapies such as aspirin, dipyridamole or clopidogrel might reduce the risk of stroke in these patients with an acceptable risk of bleeding. J Med Cases. 2015;6(10):463-467 doi: http://dx.doi.org/10.14740/jmc2289w