Cardiovascular events such as heart failure and left ventricular dysfunction (LVF); current cardiac disease, risk factors for cardiac failure, or a history of renal failure are adverse effects to assess for in patients treated with these kinase inhibitors.

In the setting of imatinib for GIST, watch for signs and symptoms consistent with cardiac or renal failure and initate appropriate treatment. Most cases of congestive heart failure and left ventricular dysfunction were reported in patients with comorbidities known to be risk factors for cardiovascular events, such as advanced age or previous medical history of cardiac disease. Clinicians should watch for signs and symptoms consistent with cardiac or renal failure and treat accordingly.1

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Withhold regorafenib in patients with GI cancers if new or acute cardiac ischemia or infarction develops. Treatment can be resumed after resolution of symptoms, if the potential benefits outweigh the risks of future cardiac ischemia.3

In patients receiving sunitinib presenting with clinical manifestations of congestive heart failure, discontinuation of treatment is recommended. Patients who experience declines in left ventricular ejection fraction (LVEF) may need treatment with an antihypertensive or diuretic.2

Because clinical trials excluded patients who presented with cardiac events within 12 months prior to administration of sunitinib, whether patients with concomitant cardiovascular conditions are at higher risk of developing drug-related LVEF is not known. Clinicians are advised to perform baseline and periodic evaluations of LVEF during treatment, including a baseline evaluation of ejection fraction in patients without cardiac risk factors.2

Additional cardiovascular-related cautions include patients with a history of QT interval prolongation, those taking antiarrhythmics, or those with preexisting cardiac disease, bradycardia, or electrolyte disturbances. Monitoring patients receiving sunitinib with on-treatment electrocardiography and laboratory measures of electrolytes should be considered.2

Hypertension incidence is increased in patients receiving regorafenib, with onset during the first cycle in most of those who develop the condition. Regorafenib should not be initiated in patients whose blood pressure is not adequately controlled. Blood pressure should be monitored weekly for the first 6 weeks then every cycle, or more frequently as indicated. The drug may need to be withheld temporarily or permanently if severe or uncontrolled hypertension develops.3