Recurrent myocardial infarction associated with gefitinib therapy.

Gefitinib is an epidermal growth factor tyrosine kinase inhibitor used as a targeted chemotherapeutic agent in the treatment of lung cancer and other solid malignancies. Unlike other tyrosine kinase inhibitors, gefitinib is not recognized as having significant cardiotoxicity though it has been reported to be capable of potentiating ADP-induced activation and thromboxane A(2) generation in platelets which could promote thrombosis. We report a case of recurrent myocardial infarction with angiographically documented vulnerable plaque rupture in a patient receiving chronic gefitinib therapy for metastatic carcinoid tumor. Platelet function studies revealed marked ADP-induced platelet activation that was only suppressed by high-dose clopidogrel. Measurement of urine 11-dehydro-thromboxane B(2) also indicated persistent thromboxane A(2) generation despite aspirin therapy, an emerging risk factor for adverse cardiovascular events.