Dose-escalation models for combination phase I trials in oncology

Designing combination drug phase I trials has become increasingly complex due to the increasing diversity in classes of agents mechanisms of action safety profiles and drug administration schedules With approximately 850 agents currently in development for cancer treatment it is evident that combination development must be prioritised as based on a specific hypothesis as well as a projected development path for the involved combination In this manuscript the most relevant issues and pitfalls for combination drug phase I trial design are discussed Several phase I study designs that incorporate controls to circumvent bias due to imbalances in observed background toxicity are discussed (C) 2010 Elsevier Ltd All rights reserved