Dose-finding with two agents in Phase I oncology trials

Biometrics. 2003 Sep;59(3):487-96. doi: 10.1111/1541-0420.00058.

Abstract

We propose an adaptive two-stage Bayesian design for finding one or more acceptable dose combinations of two cytotoxic agents used together in a Phase I clinical trial. The method requires that each of the two agents has been studied previously as a single agent, which is almost invariably the case in practice. A parametric model is assumed for the probability of toxicity as a function of the two doses. Informative priors for parameters characterizing the single-agent toxicity probability curves are either elicited from the physician(s) planning the trial or obtained from historical data, and vague priors are assumed for parameters characterizing two-agent interactions. A method for eliciting the single-agent parameter priors is described. The design is applied to a trial of gemcitabine and cyclophosphamide, and a simulation study is presented.

MeSH terms

  • Algorithms
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bayes Theorem
  • Biometry
  • Clinical Trials, Phase I as Topic / statistics & numerical data*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Interactions
  • Gemcitabine
  • Humans
  • Models, Statistical
  • Neoplasms / drug therapy*

Substances

  • Deoxycytidine
  • Cyclophosphamide
  • Gemcitabine