Dose-escalation models for combination phase I trials in oncology

Paul Hamberg; Mark J Ratain; Emmanuel Lesaffre; Jaap Verweij

doi:10.1016/j.ejca.2010.07.002

Dose-escalation models for combination phase I trials in oncology

Eur J Cancer. 2010 Nov;46(16):2870-8. doi: 10.1016/j.ejca.2010.07.002. Epub 2010 Aug 4.

Authors

Paul Hamberg¹, Mark J Ratain, Emmanuel Lesaffre, Jaap Verweij

Affiliation

¹ Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. a.hamberg@erasmusmc.nl

PMID: 20691584
DOI: 10.1016/j.ejca.2010.07.002

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.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Clinical Trials, Phase I as Topic / methods*
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Design
Drug Interactions
Drug Screening Assays, Antitumor
Humans
Models, Biological
Research Design
Toxicity Tests