Phase I Testing: 60 Years in the Making

摘要

This CCR Focus had its genesis in a workshop cosponsored by the FDA and the American Association for Cancer Research that was held in May 2015. The participants were inspired by the discussion of new ideas for early-phase drug testing, and hopeful that appropriate dosing for new molecular entities could be better identified. This CCR Focus, with Guest Editors Pasi J?anne and Amy McKee, looks at new approaches for optimizing the dosing of anticancer agents. The need to address the issue of appropriate dosing is underscored by the high rates of discontinuation in several recent registration studies that supported FDA approvals. This meant that for several of the 30 kinase inhibitors approved by the FDA, much work remained to determine the optimal dosing. Thus, the FDA posed the question of how to gain accurate, safe, and effective dosing information as early as possible. The challenge, of course, is how to accomplish this with our current phase I approach, which, although it has served physicians and patients well, is in need of some revamping. The size and complexity of our 6 0-year-old clinical trial system has made it somewhat less flexible than many would like, which explains why a description of phase I and II trials written by Farber and colleagues (1) 60 years ago still applies: