The Role Of The Electrocardiogram (Ecg) In Phase I Drug Development In Patients With Cancer: The University Of Texas M. D. Anderson Cancer Center Experience With 8,966 Ecgs.

2545 Background: Cardiac sequelae resulting from oncologic drug use are an important consideration in early cancer drug development. Recently, the focus on cardiac monitoring has increased substantially. Prolongation of the QT interval (QTc) by non-cardiac drugs is the most common cause of drug development delays, non-approvals and, in diseases other than cancer, post-marketing withdrawals by the US Food and Drug Administration. Methods: We analyzed 8,966 electrocardiograms (ECGs) performed on 598 consecutive patients with cancer who were enrolled in 22 Phase I clinical trials starting on January 1, 2006 in the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center. Results: Thirty-three ECGs (0.36 % of the total ECGs, 95%CI: 0.3% - 0.5%) from 8 patients (1.3%, 95%CI:0.7% - 2.6%) showed QTc intervals above the upper limit of normal after starting treatment. In 3 of these ECGs (2 patients) the QTc were prolonged at baseline. All QTc prolongations were deemed clinically insignificant and drug was continued without adverse sequelae. Two of 598 patients (0.33%) experienced cardiac serious adverse events (myocardial infarction (MI) and atrial flutter with hypotension (attributable to metastatic tumor to the heart)); five patients demonstrated an asymptomatic drop in ejection fraction without associated ECG findings. The patient with MI presented with dyspnea on day 2 of study, and was diagnosed on a clinical, not protocol-dictated ECGs base (non-ST elevated MI). Conclusions: Frequent monitoring with serial ECGs did not provide clinically significant information.