ABSTRACT
The main goal in phase I trials for traditional cytotoxic agents is to determine the maximal tolerated dose (MTD). The underlying premise is that both efficacy and toxicity increase monotonically with increasing dose levels. Only toxicity, not efficacy, is monitored during a traditional phase I trial. The standard 3 + 3 design accrues three to six patients at a time to a given dose level and then increases the dose level until dose limiting toxicity (DLT) is observed. If two or more DLTs are observed in a group of six patients at that dose level, dose escalation ceases and the MTD has been exceeded. The highest dose where no more than one DLT in six subjects is observed is the MTD. Storer reviews the performance of this and other traditional phase I trial designs in the first chapter of this handbook [9].
