Abstract 346P
Background
Capecitabine, an oral pro-drug of 5-fluorouracil, is part of the standard treatment of colorectal cancer (CRC). Severe adverse drug reactions that impair treatment safety remain a relevant concern. Hand-foot-syndrome (HFS) is the most frequently reported dose-limiting side effect of capecitabine. Genotyping of 4 variants of the DPYD gene is currently standard practice for capecitabine-related toxicity prediction. However, numerous studies have reported that single nucleotide polymorphisms (SNPs) in genes of capecitabine activation pathway (CES1, CES1P1, CES2, CDA, TYMP) may also contribute to individual variation in toxicity. The aim of this study was to evaluate the association of these SNPs with severe toxicity in CRC patients under capecitabine-based chemotherapy.
Methods
A prospective cohort study was conducted including 101 CRC patients under capecitabine-based chemotherapy. DNA was extracted from buccal swabs. SNPs were analyzed by real-time PCR with TaqMan probes. Sociodemographic and clinical data were obtained from medical records. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events v.5.0 in terms of mild (grade<3) or severe (grade≥3) overall toxicity and hand-foot syndrome (HFS). Bivariate analysis was used to evaluate the correlation between SNPs and toxicity.
Results
39.60% of patients were woman, median age was 63 ±11 years, major stages were IIIB-IV (80.20%) and 19.80% were treated in metastatic-setting. Severe overall toxicity was observed in 49.50% of patients and 4.95% experienced severe HFS. Metastatic setting patients (p = 0.014; OR = 3.75; CI95% = 1.31 - 12.43) showed higher risk of severe overall toxicity. CES1P1 rs11861118-CT genotype was associated with higher risk of severe overall toxicity (p = 0.008; OR = 3.43; CI95% = 1.15 - 11.03 for CT vs TT). A significant association with CES1 rs71647871-T allele and HFS was found (p = 0.019; OR = 20.67; CI95% = 2.16 - 185.98). No influence was found of SNPs in CES2, CDA and TYMP on capecitabine-based chemotherapy toxicity.
Conclusions
SNPs CES1P1 rs11861118 and CES1 rs71647871 may act as predictive biomarkers of severe overall toxicity and HFS in CRC patients under capecitabine-based therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospital Universitario Virgen de las Nieves.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.