The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy
Germline polymorphisms are inherited genetic variations present in all cells of the body.
Mounting evidence has shown that genetic polymorphisms in drug metabolizing, transporter and
targets genes are major determinants of response to drugs.
The aims of this study are to compare (i) the toxicity profile and efficacy of
gemcitabine/carboplatin or docetaxel, (ii) the distribution of genes involved in docetaxel
and gemcitabine pathways and (iii) to evaluate the association between pharmacogenetics,
pharmacokinetics and pharmacodynamics in East Asian and Caucasian patients.
To date, most pharmacogenetic strategies are predominantly focused on the role of single
genes, in the regulation of drug metabolism. However, there is clear evidence that treatment
outcomes are under the control of a network of genes, each contributing to the patient's
phenotype. In this study, we propose taking a global approach to include relevant candidate
genes in drug pathways to evaluate the effect of polymorphisms and treatment outcomes. We
have selected two commonly used chemotherapy regimens based on our previous observation of
interethnic variability in treatment outcomes and candidate polymorphisms.
By incorporating pharmacokinetic (drug level, drug elimination etc), pharmacodynamic
(treatment response, survival etc) and pharmacogenetic approaches in clinical trials, it
would enhance our understanding of the inter-individual variability in response and toxicity
to drug treatment, and is the first step towards individualized drug treatment.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]
Wei Peng Yong, MRCP, MB ChB
National University Hospital, Singapore
Singapore: Domain Specific Review Boards