Dose escalation with overdose control using a quasi-continuous toxicity score in cancer Phase I clinical trials

Zhengjia Chen, Mourad Tighiouart, Jeanne Kowalski

Research output: Contribution to journalArticlepeer-review

Abstract

Escalation with overdose control (EWOC) is a Bayesian adaptive design for selecting dose levels in cancer Phase I clinical trials while controlling the posterior probability of exceeding the maximum tolerated dose (MTD). EWOC has been used by clinicians to design many cancer Phase I clinical trials, see e.g. [1-4]. However, this design treats the toxicity response as a binary indicator of dose limiting toxicity (DLT) and does not account for the number and specific grades of toxicities experienced by patients during the trial. Chen et al. (2010) proposed a novel toxicity score system to fully utilize all toxicity information using a normalized equivalent toxicity score (NETS). In this paper, we propose to incorporate NETS into EWOC using a quasi-Bernoulli likelihood approach to design cancer Phase I clinical trials. We call the design escalation with overdose control using normalized equivalent toxicity score (EWOC-NETS). Simulation results show that this design has good operating characteristics and improves the accuracy of MTD, trial efficiency, therapeutic effect, and overdose control relative to EWOC which is used as a representative of designs treating toxicity response as a binary indicator of DLT. We illustrate the performance of this design using real trial data in identifying the Phase II dose.

Original languageEnglish (US)
Pages (from-to)949-958
Number of pages10
JournalContemporary Clinical Trials
Volume33
Issue number5
DOIs
StatePublished - Sep 2012

Keywords

  • Escalation with overdose control
  • Maximum tolerated dose
  • Multiple toxicities
  • Normalized equivalent toxicity score
  • Quasi-continuous
  • Toxicity score system

ASJC Scopus subject areas

  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Dose escalation with overdose control using a quasi-continuous toxicity score in cancer Phase I clinical trials'. Together they form a unique fingerprint.

Cite this