Tham2008 - PDmodel, Tumour shrinkage by gemcitabine and carboplatin
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ABSTRACT:
Tham2008 - PDmodel, Tumour shrinkage by gemcitabine and carboplatin
This model is described in the article:
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.
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.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000234.
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To the extent possible under law, all copyright and related or
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DISEASE(S): Lung Cancer
SUBMITTER: 
Nick Holford
PROVIDER: BIOMD0000000234 | BioModels | 2009-11-16
REPOSITORIES: BioModels
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