EXPLORING THE ROLE OF PHARMACOKINETIC ALTERATIONS IN TYROSINE KINASE INHIBITORS (TKIS)-ASSOCIATED TOXICITIES

Abstract

The advent of molecular targeted therapy in the late 1990s marks a major breakthrough in the fight against cancer. While the use of tyrosine kinase inhibitors (TKIs) have largely mitigated the conventional toxicities of chemotherapeutic agents, a range of previously unknown and sometimes unpredictable toxicities like cutaneous, cardiac and liver toxicities began to surface. Furthermore, several new issues such as the tailoring of cancer treatment to an individual patient, assessing patient adherence to therapy and evaluating drug effectiveness and toxicity are raised with these novel targeted therapies. Therefore, the overall aim of this thesis is to evaluate how pharmacokinetic alterations in TKIs can contribute to toxicities, by focusing on three main themes of drug exposure, genetic polymorphism and drug-drug interactions. It is important that these issues with toxicities are addressed to improve the management of anticancer therapy in patients so as to optimize risk/benefit ratio of these therapies.