%0 Journal Article
%T Disruptions in Liver Function among Cancer Patients and Patients Treated with Tyrosine Kinase Inhibiting Drugs: Comparisons of Two Population-Based Databases
%A Sarah H. Landis
%A Beth L. Nordstrom
%A Leah B. Sansbury
%A Sumitra Shantakumar
%A Samantha A. St. Laurent
%A Kathy H. Fraeman
%A Jeanenne J. Nelson
%J Journal of Cancer Epidemiology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/358285
%X Liver toxicity is a recognized adverse event associated with small molecule tyrosine kinase inhibitors (TKIs). Electronic Medical Record (EMR) databases offer the most precise data to investigate the rate of liver function test (LFT) elevations; however, they can be limited in sample size and costly to access and analyze. Health insurance claims databases often contain larger samples sizes but may lack key health information. We evaluated the feasibility of utilizing a large claims database to calculate incidence rates (IRs) of LFT elevations among a general cohort of cancer patients and a cohort of patients treated with TKIs by comparing the results to a ˇ°gold standardˇ± oncology-specific EMR database. IRs for the TKI cohorts were very similar between the two databases; however, IRs were higher in the EMR database for the cancer cohorts. Possible explanations for these differences include lack of specificity when defining a cancer case, poor capture of laboratory data, or inaccurate assessment of person-time in the insurance claims database. This study suggests that insurance claims data may provide reliable results when investigating liver toxicities associated with oncology drug exposure; however, there are limitations when assessing laboratory outcomes for cohorts defined solely by disease status. 1. Introduction Therapeutic agents that target cancer-specific molecules and signalling pathways have become increasingly integrated into cancer care in recent years. Activation of tyrosine kinases plays a critical role in modulation of growth factor signalling, such as increased cell proliferation and growth, induced antiapoptotic effects, and promotion of angiogenesis and metastasis, and as a result, these protein kinases are key targets for inhibition [1, 2]. Tyrosine kinases can be further classified as receptor kinases and nonreceptor protein kinases [2]. Small-molecule inhibitors of tyrosine kinase target a number of receptors, including BCR-ABLE, c-KIT, PDGFR, EGFR, and FLT-3 [2]. Currently, there are six small molecule TKIs approved by the FDA: imatinib (Gleevec, Glivec), gefitinib (Iressa), erlotinib (Tarceva), dasatinib (Sprycel), lapatinib (Tykerb, Tyverb), and nilotinib (Tasigna). The liver plays a major part in metabolic and excretory functions, including a key role in the metabolism of a number of anticancer cytotoxics and biologic agents, causing drug inactivation or activation of a prodrug. In turn, chemotherapy and biological agents can induce liver injury or dysfunction, which can manifest in abnormal serum liver biochemistry [3].
%U http://www.hindawi.com/journals/jce/2013/358285/