DDMODEL00000261: Wilbaux_2015_KPD_CTC.count_PSA

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Short description:
The purpose of this model was to quantify the dynamic relationships between the longitudinal kinetics of circulating tumor cells (CTCs) and PSA during treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Data from 223 patients with mCRPC treated by chemotherapy and/or hormonotherapy were analyzed for up to 6 months of treatment. A semimechanistic model was built, combining the following several pharmacometric advanced features: (1) Kinetic-Pharmacodynamic (K-PD) compartments for treatments (chemotherapy and hormonotherapy); (2) a latent variable linking both marker kinetics; (3) modeling of CTC kinetics with a cell lifespan model; and (4) a negative binomial distribution for the CTC random sampling.
Original code
  • A Joint Model for the Kinetics of CTC Count and PSA Concentration During Treatment in Metastatic Castration-Resistant Prostate Cancer.
  • Wilbaux M, Tod M, De Bono J, Lorente D, Mateo J, Freyer G, You B, Hénin E
  • CPT: Pharmacometrics & Systems Pharmacology, 5/2015, Volume 4, Issue 5, pages: 277-285
  • EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1 Oullins, France.
  • Assessment of treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) is limited by frequent nonmeasurable bone metastases. The count of circulating tumor cells (CTCs) is a promising surrogate marker that may replace the widely used prostate-specific antigen (PSA). The purpose of this study was to quantify the dynamic relationships between the longitudinal kinetics of these markers during treatment in patients with mCRPC. Data from 223 patients with mCRPC treated by chemotherapy and/or hormonotherapy were analyzed for up to 6 months of treatment. A semimechanistic model was built, combining the following several pharmacometric advanced features: (1) Kinetic-Pharmacodynamic (K-PD) compartments for treatments (chemotherapy and hormonotherapy); (2) a latent variable linking both marker kinetics; (3) modeling of CTC kinetics with a cell lifespan model; and (4) a negative binomial distribution for the CTC random sampling. Linked with survival, this model would potentially be useful for predicting treatment efficacy during drug development or for therapeutic adjustment in treated patients.
Melanie Wilbaux
Context of model development: Clinical end-point;
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: Assessment of treatment efficacy in metastatic castrationresistant prostate cancer (mCRPC) is limited by the frequent development of nonmeasurable bone metastases. The count of circulating tumor cells (CTCs) is emerging as a promising surrogate marker, which could replace the widely used prostate-specific antigen (PSA). CTC kinetic monitoring during treatment could be used to predict treatment efficacy in patients with mCRPC. However, relationships between the kinetics of CTCs and PSA have never been assessed. We built a semimechanistic population model of CTC and PSA kinetics during treatment.;
Modelling task in scope: estimation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Oncology;
Annotations are correct.
This model is not certified.
  • Model owner: Melanie Wilbaux
  • Submitted: Oct 22, 2017 1:13:56 PM
  • Last Modified: Oct 22, 2017 1:13:56 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Oct 22, 2017 1:13:56 PM
    • Submitted by: Melanie Wilbaux
    • With comment: Updated model annotations.
 
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