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A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients.


ABSTRACT: Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE). We present a modeling and simulation framework for the most common erlotinib-induced AE, rash, and diarrhea, providing insights into erlotinib toxicity. We used the framework to investigate the safety of high-dose erlotinib pulses proposed to limit acquired resistance while treating NSCLC. Continuous-time Markov models were developed using rash and diarrhea AE data from 39 NSCLC patients treated with erlotinib (150 mg/day). Exposure and different covariates were investigated as predictors of variability. Rash was also tested as a survival predictor. Models developed were used in a simulation analysis to compare the toxicities of different regimens, including the previously mentioned pulsed strategy. Probabilities of experiencing rash or diarrhea were found to be highest early during treatment. Rash, but not diarrhea, was positively correlated with erlotinib exposure. In contrast with some common understandings, radiotherapy decreased transitioning to higher rash grades by 81% (p?

SUBMITTER: Suleiman AA 

PROVIDER: S-EPMC4627460 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients.

Suleiman Ahmed Abbas AA   Frechen Sebastian S   Scheffler Matthias M   Zander Thomas T   Nogova Lucia L   Kocher Martin M   Jaehde Ulrich U   Wolf Jürgen J   Fuhr Uwe U  

The AAPS journal 20150819 6


Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE). We present a modeling and simulation framework for the most common erlotinib-induced AE, rash, and diarrhea, providing insights into erlotinib toxicity. We used the framework to investigate the safety of high-dose erlotinib pulses proposed to limit acquired resistance while treating NSCLC  ...[more]

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