title: A Bayesian case study in oncology Phase I combination dose-finding using logistic regression with covariates.
abstract: A Bayesian approach to finding the maximum tolerated dose (MTD) is presented. The approach is flexible, allowing inclusion of covariates, and enables transparent dose recommendations based on comprehensive inferential summaries on the probability of dose-limiting toxicities (DLT). A case study is presented for a Phase I combination of two oncology drugs, nilotinib and imatinib. Data obtained and decisions made during the study are described. Final determination of the MTD pair is outlined, along with discussion regarding the use and interpretability of within- and end-of-study data.
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. stuart.bailey@novartis.com
authors.forename: Stuart
authors.initials: S
authors.lastname: Bailey
authors.forename: Beat
authors.initials: B
authors.lastname: Neuenschwander
authors.forename: Glen
authors.initials: G
authors.lastname: Laird
authors.forename: Michael
authors.initials: M
authors.lastname: Branson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001499:Bayes Theorem; D001549:Benzamides; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D000068877:Imatinib Mesylate; D016015:Logistic Models; D020714:Maximum Tolerated Dose; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011336:Probability; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib