title: Modeling antitumor activity by using a non-linear mixed-effects model.
abstract: The response of solid tumors to antitumor treatment generally declines markedly with treatment time. Sometimes, a tumor regrows (rebounds) before the end of the treatment period. Studies of the patterns of tumor response to treatment are important, because they may provide useful information for clinical decision-making. We have investigated patterns of tumor response in mouse xenograft tumors by using data from a study conducted at St. Jude Children's Research Hospital. We applied a biexponential non-linear mixed-effects model to an analysis of changes in tumor volume over a given period of treatment. The model gives a good fit to the data, even for small sample sizes. We addressed the relation between the baseline tumor volumes and the decay rates of the first and second stages of the tumor's response to treatment, and we applied sensitive analysis to determine the effect of using different imputed values for missing data. We also proposed a novel approach to a comparison of the antitumor effects of three different treatments, and we used the data from a St. Jude study to demonstrate the potential of this comparison approach in cancer clinical decision-making.
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105-2794, USA. hua.liang@stjude.org
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.forename: Naijun
authors.initials: N
authors.lastname: Sha
mesh_terms: D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003198:Computer Simulation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D017711:Nonlinear Dynamics; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D000077204:Temozolomide; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide