Cancer has been the leading cause of death for over thirty years in Taiwan and remains a major challenge in medicine. Traditionally, surgical resection, systemic chemotherapy and radiation therapy are three main treatment options. With advances in oncological field, more and more novel anti-cancer therapies are developed, and treatments are moving towards "precision medicine". Today, many cancers have been found to be associated with abnormal gene expression or molecular signaling pathways, leading to the development of targeted therapy. Many oral small molecule targeted drugs have been developed as a result and the development of these oral targeted drugs not only offers greater convenience for patients who can receive tumor treatment without hospitalization, but their side effects are also lower than those of traditional chemotherapy.
Tyrosine kinase inhibitors (TKIs) are drugs that can block tyrosine kinases, and are the prototype of targeted therapy. In the human body, the tyrosine kinase family accounts for only a small proportion of protein kinases, but a higher proportion in oncogenes. Till now, a variety of tyrosine kinase inhibitors have already been developed and launched in market, such as imatinib, dasatinib, nilotinib, gefitinib, erlotinib, afatinib, osimertinib, regorafenib, sunitinib, lenvatinib and sorafenib. Each of them has different mechanism of action and each of them is used for different types of cancer. Just like other drugs, the doses of TKIs are determined based on pivotal clinical trials, with the same doses used regardless of differences in ethnicity, gender, or body size. This is different from traditional chemotherapy or monoclonal antibody drugs, which are dosed based on body surface area or weight. Additionally, the majority of participants in these pivotal clinical trials are Caucasian, with a very low representation of East Asians who typically have smaller body sizes. However, the differences in race and body size are closely related to drug metabolism. The use of fixed-dose regimens does indeed overlook many differences between ethnic groups. For example, Asians may be exposed to higher concentrations of drugs than Caucasians at the same dose, which could affect efficacy and side effects.
In light of this, we are conducting a pharmacokinetic analysis studies on the Taiwanese population for nine commonly used tyrosine kinase inhibitors (afatinib, dasatinib, imatinib, lenvatinib, nilotinib, osimertinib, regorafenib, sunitinb and sorafenib) in relation to their corresponding cancer types (non-small cell lung cancer, head and neck cancer, gastrointestinal stromal tumor, renal cell carcinoma, chronic myeloid leukemia, hepatocellular carcinoma, colorectal cancer). We collected serum pharmacokinetic data from real patients before/after medication to analyze pre- and post-dosing drug and metabolite concentrations using nonlinear mixed-effect model software (NONMEM), and to calculate the correlation between population pharmacokinetics, clinical efficacy and toxicity. Using these data, we could survey the more appropriate dosage and finding the most suitable treatment strategies for Taiwanese population.
Application and Highlights:
1.Investigation of pharmacokinetics of common tyrosine kinase inhibitors in Taiwanese population.
2.Determination of optimal drug dosages for Taiwanese population to reduce medication-related side effects.
Research Team Members: Tsung-Jang Yeh, Li-Tzong Chen, Jaw-Yuan Wang, I-Chen Wu, Yaw-Bin Huang
Representative Department: Center for Cancer Research
Introduction of Research Team: Our team belongs to the Cancer Research Center. We started by addressing common issues in clinical care for cancer patients and combined with the professional analysis of our pharmacy team. Our ultimate goal is to provide more suitable dosage prescriptions for cancer patients using tyrosine kinase inhibitors and to find the most appropriate treatment plan for Taiwanese populations.
Contact Email: 1030307@kmuh.org.tw