A PHARMACOGENETIC STUDY OF CAPECITABINE-OXALIPLATIN THERAPY IN COLORECTAL CANCER PATIENTS AMONG SOUTH INDIAN POPULATION

S. Ramalakshmi*, S. Kavimani, Satish Srineevas, V. Vettriselvi and LVK S Bhaskar

ABSTRACT

Capecitabine with oxaliplatin (CAPOX) is considered to be a standard treatment option in colorectal cancer (CRC) therapy. The limitation associated with the use of these anticancer drugs is the unpredictable interindividual variation in efficacy and toxicity. However, variability in treatment outcome for the multiple chemotherapeutic regimens has been attributed to genetic factors. Hence, this study analyzed the effect of TS, MTHFR, DPD and GSTP1 gene polymorphism on toxicity and efficacy in CRC patients on CAPOX therapy. Sixteen patients between 18-75yrs of age on CAPOX therapy were included in the study. The genomic DNA was isolated from the peripheral blood and was genotyped using PCR RFLP method. No relationships between TYMS, MTHFR, DPD, GSTP1 genotypes, and global toxicity were observed on univariate Fisher's exact tests. However, exon 14 skipping IV +1g>A which is related to DPD deficiency occurred in only 1of 16 patients with more toxic side effects. In patients carrying val/val GSTP1 Exon 5 genotype, Grade 2 cumulative peripheral neuropathy was observed relative to the other (1of 4 patients, 25%).Three patients with 2R/2R genotype were non responders. One patient was heterozygous for TS, MTHFR677, MTHFR 1298 and GSTP1 and had a poor prognosis .The present data indicates that the patients with 2R/2R were not good candidates for CAPOX therapy. Further, DPD deficiency and GSTP1 polymorphism should be observed for patients receiving CAPOX therapy. A larger data set is required for confirmation as such information would allow individualization of chemotherapy and maintaining quality of life.

Keywords: Pharmacogenomics, Colorectal cancer, Capecitabine. Oxaliplatin.