Annals of oncology : official journal of the European Society for Medical Oncology
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The primary goal of phase I studies is to efficiently and accurately determine the recommended dose of a new agent for further investigation. Issues of concern ranging from the ethics of these trials to selection of starting dose and rapidity of dose escalation, have led to suggested modifications of the traditional phase I design. We wanted to assess the frequency with which these new approaches are being applied to recent phase I trials and, if possible, their impact. ⋯ Despite proposed new methodologies (particularly dose escalation) for phase I trials, very few are being employed in practice. A concerted effort should be made to prospectively evaluate these to determine which provides the best combination of safety and efficacy. In addition, the lack of standardization in the definition of limiting toxicity is surprising. Those involved in drug development should strive for agreement on the acceptable degree of toxicity for phase II dose selection.