Modeling antitumor activity in xenograft tumor treatment.
To analyze responses of solid tumors to treatment with antitumor therapy, we applied nonparametric mixed-effects models to investigate tumor volumes measured over a fixed. The population and individual response functions were approximated by penalized splines. Linear mixed-effects modeling was applied in the implementation of the estimation. We applied the approach to an analysis of a real xenograft study of a new antitumor agent, temozolomide, combined with irinotecan. The model fitted the data very well. We conducted a sensitivity analysis to determine the effect of informative dropout. We also propose an intuitive approach to a comparison of the antitumor effects of two different treatments. Biological interpretations and clinical implications are discussed.
Liang
Hua
H
St. Jude Children's Research Hospital, USA. hua.liang@stjude.org
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003198:Computer Simulation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D000077146:Irinotecan; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D000077204:Temozolomide; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide