Dose-escalation models for combination phase i trials in oncology
November 2010
Article
volume 46, issue 16 pp 2870-2878.
| Related Files |
|---|
|
Redirect to Publisher's version
(Publisher's version.url.txt, 44 bytes) |
Repository contains one additional file which is not publicly available
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.
Keywords
- human
- methodology
- priority journal
- clinical trial
- oncology
- feasibility study
- carboplatin
- paclitaxel
- review
- treatment duration
- dose response
- doxorubicin
- cardiotoxicity
- drug dose escalation
- Bayesian
- alkylating agent
- drug mechanism
- Phase I
- febrile neutropenia
- radiation dose
- etoposide
- taxane derivative
- model
- oxaliplatin
- clinical research
- drug potentiation
- docetaxel
- leukemogenesis
- maximum tolerated dose
- phase 1 clinical trial
- Bayesian learning
- Combination
- Controls
- Dose-escalation
- Trial design
- combination drug phase 1 trial
- neuropathy
- nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
