Dose-finding with two agents in Phase I oncology trials.
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.
Thall
Peter F
PF
Department of Biostatistics, Box 447, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA. rex@mdanderson.org
Millikan
Randall E
RE
Mueller
Peter
P
Lee
Sang-Joon
SJ
D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001499:Bayes Theorem; D001699:Biometry; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004347:Drug Interactions; D006801:Humans; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D003520:Cyclophosphamide; D000093542:Gemcitabine