A RARE ADVERSE EVENT

Clin Cancer Res. 2011 Aug 3. [Epub ahead of print]

Thrombotic Microangiopathy with Targeted Cancer Agents.

Blake-Haskins JA, Lechleider RJ, Kreitman RJ.

Source

Clinical Development, MedImmune, LLC.

Abstract

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are clinically similar disorders characterized by microvascular thrombosis, hemolysis, thrombocytopenia, and end organ damage. Although they may present with overlapping symptoms, multiple etiologies have been proposed for these thrombotic microangiopathies (TMAs). Chemotherapy-induced TMA has been described with the use of mitomycin, gemcitabine, and others and has a poor prognosis. Recently, reports of TMA associated with targeted cancer agents have surfaced in the literature. We discuss the clinical presentation, outcome, and etiology of TMA reported with the use of immunotoxins, monoclonal antibodies, and tyrosine kinase inhibitors. A search of PubMed and meeting abstracts was conducted for cases of TMA with the use of targeted cancer agents. The defining symptoms, laboratory values, time to onset, and patient outcomes were compiled. Consistent definitions of TMA and grading of severity in these cases are lacking. However, presentation of TMA in these cases revealed the importance of monitoring for renal toxicity, hemolysis, and thrombocytopenia. Patient outcomes appear to differ from those seen in cases of chemotherapy-induced TMA and may reflect a different underlying etiology. Little is known about the pathogenesis of TMA with targeted cancer agents. In contrast to chemotherapy-induced TMA, partial to full reversibility may be a common outcome. However, further research is warranted into optimal management of patients diagnosed with TMA following treatment with targeted agents.