title: Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate Cancer in Patients Treated With Eribulin.
abstract: Frameworks that associate cancer dynamic disease progression models with parametric survival models for clinical outcome have recently been proposed to support decision making in early clinical development. Here we developed such a disease progression clinical outcome model for castration-resistant prostate cancer (CRPC) using historical phase II data of the anticancer agent eribulin. Disease progression was captured using the dynamics of prostate-specific antigen (PSA). For clinical outcome, overall survival (OS) was used. The model for PSA dynamics comprised parameters for baseline PSA (23.2 ng/ml, relative standard error (RSE) 16.5%), growth rate (0.00879 day(-1), RSE 12.6%), drug effect (0.241 µg·h·l(-1) day(-1), RSE 32.6%), and resistance development (0.0113 day(-1), RSE 44.3%). OS was modeled according to a Weibull distribution. Predictors for survival included model-predicted PSA time to nadir (TTN), PSA growth rate, Eastern Cooperative Oncology Group (ECOG) score, and baseline PSA. The developed framework can be considered to support informative design and analysis of drugs developed for CRPC.
authors: Department of Clinical Pharmacology, Netherlands Cancer Institute Amsterdam, The Netherlands ; Department of Pharmacy & Pharmacology, Netherlands Cancer Institute Amsterdam, The Netherlands ; Division of Pharmacology, Cluster Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University Leiden, The Netherlands.
authors: J G C
authors: JG
authors: van Hasselt
authors: Eisai Limited Hatfield, UK.
authors: A
authors: A
authors: Gupta
authors: Eisai Limited Hatfield, UK.
authors: Z
authors: Z
authors: Hussein
authors: Department of Clinical Pharmacology, Netherlands Cancer Institute Amsterdam, The Netherlands ; Faculty of Science, Department of Pharmaceutical Sciences, Division of Clinical Pharmacology and Pharmacoepidemiology, Utrecht University Utrecht, The Netherlands.
authors: J H
authors: JH
authors: Beijnen
authors: Department of Pharmacy & Pharmacology, Netherlands Cancer Institute Amsterdam, The Netherlands ; Faculty of Science, Department of Pharmaceutical Sciences, Division of Clinical Pharmacology and Pharmacoepidemiology, Utrecht University Utrecht, The Netherlands.
authors: J H M
authors: JH
authors: Schellens
authors: Department of Clinical Pharmacology, Netherlands Cancer Institute Amsterdam, The Netherlands ; Department of Pharmacy & Pharmacology, Netherlands Cancer Institute Amsterdam, The Netherlands.
authors: A D R
authors: AD
authors: Huitema