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Updated: Jun 10, 2026

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
Dose-escalation models for combination phase I trials in oncology
Paul Hamberg1, Mark J Ratain, Emmanuel Lesaffre
1Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. a.hamberg@erasmusmc.nl
Abstract:
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.
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