Phase I Trials in Oncology: Design and Endpoint

Early clinical development of anticancer drugs is beset with obstacles unique to this type of therapy. Typical healthy volunteer studies are seldom possible, and patients tend to have end-stage malignant processes, with many underlying symptoms and often organ dysfunction. This chapter will focus on the design of traditional early phase I clinical trials of anticancer therapies, including selection of patients, starting dose selection, dose-escalation approaches, and endpoints. It will go on to examine the limitations of the current, widely accepted approaches and some of the problems facing investigators. Finally, it will also discuss how early anticancer drug development now faces a paradigm shift due to the advent of novel, molecularly targeted anticancer drugs