Cardiovascular toxicity associated with small molecule tyrosine kinase inhibitors currently in clinical use

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have changed the concepts of systemic therapy for a variety of advanced solid and hematologic malignancies. However, their toxicity can be significant, and includes both cardiac and non-cardiac effects. AREAS COVERED: The authors evaluate comprehensively the adverse cardiovascular portfolio of small molecule TKIs, postulate their underlying mechanisms and offer recommendations regarding prevention and therapy of these toxicities. EXPERT OPINION: For most pan-selective TKIs, there might not be a clear-cut relationship between specific patterns of TK inhibition and cardiovascular toxicity. Cardiovascular side effects are likely due to dysregulation of multiple kinase regulated pathways. The cardiovascular effects of small molecule TKIs include peripheral edema and congestive heart failure, systemic and pulmonary hypertension, acute coronary syndromes and cardiac arrest due to QTc prolongation. Caution should be sought in patients with pre-existing cardiac dysfunction before initiating any of these agents. It is hoped that newer TKI generations will display minimal if any cardiovascular toxicity, while maintaining their anticancer efficacy. As of today, the high likelihood of morbidity without treatment mandates that cardiovascular toxicity of TKIs be carefully assessed and balanced with the known benefits of administering these agents.