Abstract
Aim:CAPOX treatment in CRC patients was reported to cause several dose-limiting toxicities, and are found responsible for treatment interruption or even discontinuation. Therefore there is a critical need for identifying the predictive biomarkers for such toxicities to prevent them. The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and GSTP1 ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with CRC. Patients and Methods:We have recruited 145 newly diagnosed and treatment naive CRC patients in the study. Each Patient received a standard treatment schedule of oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. 5 ml of the venous blood was collected from each patient and genomic DNA extraction and genotyping. The genotyping analysis of the selected genetic polymorphisms was carried out by real-time PCR using TaqMan SNP genotyping assays obtained from applied biosystems. Results:The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9A carries were found to be at higher risk for HFS, diarrhoea and thrombocytopenia when compared to patients with wild allele. No significant association was found between DPYD*6, GSTP1 ile105val polymorphisms and CAPOX related toxicities except for thrombocytopenia. Conclusion:A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker.
Highlights
The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and Glutathione-S-transferase P1 (GSTP1) ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with colorectal cancer (CRC)
A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker
Oxaliplatin-related cumulative neuropathy and neutropenia were reported to be more frequent and severe in patients with heterozygous (AG) and homozygous (GG) genotype when compared to wild allele (AA) patients (Lecomte et al, 2006; Zhong et al, 2006) The aim of our study was to find the association between DPYD and GSTP1 gene polymorphisms and toxicities with CAPOX treatment in south Indian patients with colorectal cancer
Summary
5-fluorouracil and its oral prodrug capecitabine are the widely used anticancer agents and their combination regimens with other anticancer drugs are the backbone in the treatment of various cancers like colon, rectum, breast, stomach, oesophagal and pancreatic cancer etc (Malet-Martino and Martino, 2002). The C>T replacement induces amino acid change valine to isoleucine Both these polymorphisms were reported to alter the catalytic activity of DPYD enzyme and linked with capecitabine associated toxicities. Oxaliplatin-related cumulative neuropathy and neutropenia were reported to be more frequent and severe in patients with heterozygous (AG) and homozygous (GG) genotype when compared to wild allele (AA) patients (Lecomte et al, 2006; Zhong et al, 2006) The aim of our study was to find the association between DPYD and GSTP1 gene polymorphisms and toxicities with CAPOX treatment in south Indian patients with colorectal cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
