QTc prolongation and/or oncology drug development: Who’s in danger?

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Over recent years, several non-oncological agents were removed from the market based on cardiac toxicity due to prolongation of the cardiac repolarisation, defined as prolongation of the QTc interval on the ECG, observed post registration. This resulted in enhanced regulatory attention on cardiac safety monitoring during drug development and, in May 2005, the implementation by the FDA of the E14 ‘Clinical evaluation of QT/QTC interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs’. These guidelines have been written in the light of drug development in non-oncological areas and do not take into consideration the differences in the patient population, in study design or the risk-benefit balancing relative to potential QT-liability and potential anticancer efficacy. During the development of new drugs a continuous benefit and risk assessment takes place. The involved considerations will be different and dependent on the patient population targeted. In oncology the nature and severity of the disease is such that most patients with metastatic disease will still succumb to their disease. Balancing the need for novel treatment in this area against the risks of the medical products will result in accepting more toxicity compared to other indications, as is presently the case for many standard therapeutic options in oncology. Also, the intense lobbying of patient representatives for early access to experimental drugs indicates the willingness of this patient