Tham2008 - PDmodel, Tumour shrinkage by gemcitabine and carboplatin

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Short description
Tham2008 - PDmodel, Tumour shrinkage by gemcitabine and carboplatin

This model is described in the article:

Tham LS, Wang L, Soo RA, Lee SC, Lee HS, Yong WP, Goh BC, Holford NH.
Clin. Cancer Res. 2008 Jul; 14(13): 4213-4218

Abstract:

PURPOSE: This tumor response pharmacodynamic model aims to describe primary lesion shrinkage in non-small cell lung cancer over time and determine if concentration-based exposure metrics for gemcitabine or that of its metabolites, 2',2'-difluorodeoxyuridine or gemcitabine triphosphate, are better than gemcitabine dose for prediction of individual response. EXPERIMENTAL DESIGN: Gemcitabine was given thrice weekly on days 1 and 8 in combination with carboplatin, which was given only on day 1 of every cycle. Gemcitabine amount in the body and area under the concentration-time curves of plasma gemcitabine, 2',2'-difluorodeoxyuridine, and intracellular gemcitabine triphosphate in white cells were compared to determine which best describes tumor shrinkage over time. Tumor growth kinetics were described using a Gompertz-like model. RESULTS: The apparent half-life for the effect of gemcitabine was 7.67 weeks. The tumor turnover time constant was 21.8 week.cm. Baseline tumor size and gemcitabine amount in the body to attain 50% of tumor shrinkage were estimated to be 6.66 cm and 10,600 mg. There was no evidence of relapse during treatment. CONCLUSIONS: Concentration-based exposure metrics for gemcitabine and its metabolites were no better than gemcitabine amount in predicting tumor shrinkage in primary lung cancer lesions. Gemcitabine dose-based models did marginally better than treatment-based models that ignored doses of drug administered to patients. Modeling tumor shrinkage in primary lesions can be used to quantify individual sensitivity and response to antitumor effects of anticancer drugs.

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Format
SBML (L2V4)
Related Publication
  • A pharmacodynamic model for the time course of tumor shrinkage by gemcitabine + carboplatin in non-small cell lung cancer patients.
  • Tham LS, Wang L, Soo RA, Lee SC, Lee HS, Yong WP, Goh BC, Holford NH
  • Clinical cancer research : an official journal of the American Association for Cancer Research , 7/ 2008 , Volume 14 , pages: 4213-4218
  • Department of Hematology-Oncology, National University Hospital, Singapore. Tham_lai_san@lilly.com
  • PURPOSE: This tumor response pharmacodynamic model aims to describe primary lesion shrinkage in non-small cell lung cancer over time and determine if concentration-based exposure metrics for gemcitabine or that of its metabolites, 2',2'-difluorodeoxyuridine or gemcitabine triphosphate, are better than gemcitabine dose for prediction of individual response. EXPERIMENTAL DESIGN: Gemcitabine was given thrice weekly on days 1 and 8 in combination with carboplatin, which was given only on day 1 of every cycle. Gemcitabine amount in the body and area under the concentration-time curves of plasma gemcitabine, 2',2'-difluorodeoxyuridine, and intracellular gemcitabine triphosphate in white cells were compared to determine which best describes tumor shrinkage over time. Tumor growth kinetics were described using a Gompertz-like model. RESULTS: The apparent half-life for the effect of gemcitabine was 7.67 weeks. The tumor turnover time constant was 21.8 week.cm. Baseline tumor size and gemcitabine amount in the body to attain 50% of tumor shrinkage were estimated to be 6.66 cm and 10,600 mg. There was no evidence of relapse during treatment. CONCLUSIONS: Concentration-based exposure metrics for gemcitabine and its metabolites were no better than gemcitabine amount in predicting tumor shrinkage in primary lung cancer lesions. Gemcitabine dose-based models did marginally better than treatment-based models that ignored doses of drug administered to patients. Modeling tumor shrinkage in primary lesions can be used to quantify individual sensitivity and response to antitumor effects of anticancer drugs.
Contributors
Nick Holford

Metadata information

is
BioModels Database MODEL0911120001
BioModels Database BIOMD0000000234
isDescribedBy
PubMed 18594002
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasProperty
Human Disease Ontology lung cancer
Curation status
Curated
Original model(s)
http://models.cellml.org/exposure/a073e1965c0a2e12664a19f18e810d46/tham_2008.cellml/view
  • Model originally submitted by : Nick Holford
  • Submitted: Nov 15, 2009 6:46:45 PM
  • Last Modified: May 18, 2017 12:02:23 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: May 18, 2017 12:02:23 PM
    • Submitted by: Nick Holford
    • With comment: Current version of Tham2008 - PDmodel, Tumour shrinkage by gemcitabine and carboplatin
  • Version: 1 public model Download this version
    • Submitted on: Nov 15, 2009 6:46:45 PM
    • Submitted by: Nick Holford
    • With comment: Original import of BIOMD0000000234.xml.origin
Curator's comment:
(added: 23 Nov 2009, 15:49:57, updated: 23 Nov 2009, 15:49:57)
The model reproduces figure 1 of the reference publication. The simulation was done using SBML odeSolver.