98P - Influence of DPYD*9, DPYD*6 and GSTP1 ile105val genetic polymorphisms on capecitabine and oxaliplatin (CAPOX) associated toxicities in colorectal cancer patients

Background

Capecitabine and oxaliplatin combination regimen (CAPOX) is the standard chemotherapeutic care for the treatment of colorectal cancer (CRC). CAPOX treatment is found to be equivalent to FOLFOX and FOLFRI in efficacy and preferred over them due to its easy management and convenience in administration. However, CAPOX treatment was associated with several dose-limiting toxicities and high inter-individual variation in toxicity profile. These toxicities may limit treatment effectiveness as they impose treatment interruption or even discontinuation. Therefore, there is a critical need for identifying the predictive biomarkers for CAPOX related toxicities.

Methods

Patients and methods: In an intent treat analysis, 145 CRC patients were recruited. Patients 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 was extracted by the phenol-chloroform method. The genotyping analysis of the selected SNP’s was carried out by real-time PCR using TaqMan SNP genotyping assays from applied biosystems.

Results

The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9 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.

Conclusions

A significant association was observed between DPYD*9A A>G polymorphism and CAPOX induced dose-limiting toxicities like HFS, diarrhoea and thrombocytopenia strengthening its role as a predictive biomarker.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ashok Varma.

Funding

Jawaharlal Institute of Post-Graduate Medical Education and Research (JIPMER).

Disclosure

The author has declared no conflicts of interest.