UNASSIGNED: Treatment with @entity3866 , an epidermal growth factor receptor @entity4149 kinase inhibitor used for treating @entity1149 ( @entity1149 ) and other @entity5 , is frequently associated with @entity137 ( @entity137 ). We present a modeling and simulation framework for the most common @entity3866 -induced @entity137 , @entity1910 , and @entity294 , providing insights into @entity3866 @entity137 . We used the framework to investigate the safety of high-dose @entity3866 pulses proposed to limit acquired resistance while treating @entity1149 . Continuous-time Markov models were developed using @entity1910 and @entity294 @entity137 data from 39 @entity1149 @entity1 treated with @entity3866 (150  mg/day). Exposure and different covariates were investigated as predictors of variability. @entity1910 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 @entity1910 or @entity294 were found to be highest early during treatment. @entity1910 , but not @entity294 , was positively correlated with @entity3866 exposure. In contrast with some common understandings, radiotherapy decreased transitioning to higher @entity1910 grades by 81% (p   <   0.01), and experiencing @entity1910 was not correlated with positive survival outcomes. Model simulations predicted that the proposed pulsed regimen (1600  mg/week   +   50  mg/day remaining week days) results in a maximum of 20% of the @entity1 suffering from severe @entity1910 throughout the treatment course in comparison to 12% when treated with standard dosing (150  mg/day). In conclusion, the framework demonstrated that radiotherapy attenuates @entity3866 -induced @entity1910 , providing an opportunity to use radiotherapy and @entity3866 together, and demonstrated the tolerability of high-dose pulses intended to address acquired resistance to @entity3866 .

A Modeling and Simulation Framework for Adverse Events in @entity3866 -Treated Non-Small-Cell Lung Cancer XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'AE', 'adverse events'] @entity1910 :: ('MESH:D005076', 'Disease') :: ['rash', 'Rash'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung cancer'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity3866 :: ('MESH:C400278', 'Chemical') :: ['erlotinib']
@entity1 :: (9606,Species) :: ['Patients']
