Cytidine Deaminase (CD) and Dihydropyrimidine Dehydrogenase (DPD) single nucleotide polymorphisms (SNPs) in capecitabine-treated colorectal cancer (CRC).

Abstract

3662 Background: CD is an enzyme that metabolizes 5'DeoxyFluorocytidine (5'dFCR) to 5' DeoxyFluorouridine (5'dFUR), which converts to 5-FU in the presence of Thymidine Phosphorilase (TP). The rate-limiting enzyme in 5-FU catabolims is DPD, which converts 5-FU to dihydrofluorouracil (DHFU). We analyzed CD and DPD SNPs and correlate the results with toxicity and response in capecitabine-treated CRC patients (pts) Methods: 33 CRC pts recruited between August 2002 and September 2003 were treated with capecetabine. DNA was obtained from peripheral blood cells at baseline, and allelic discrimination assay with ABI Prism 7700 was used to analyze SNPs at CD Lys27Gln, DPD1 Arg16Cys and DPD2 Ile530Val. RESULTS Pts characteristics: age 61 (44-77); all pts, PS 0-1; 26 stage IV pts received capecitabine-based combination chemotherapy, 7 stage II/III pts received capecitabine plus radiotherapy. 33 pts evaluable for toxicity. Pts with CD genotypes A/C and C/C showed greater hematological toxicity (61%) than those with A/A (29%) (p=0.08). DPD1 genotypes C/C showed greater skin toxicity (40%) than those with C/T and T/T (0%) (p=0.01). 24 stage IV pts evaluable for response. Pts with CD genotype A/A had longer median survival (11.5 mos) than those with A/C and C/C (5 m) (Gehan-Wilcoxon p=0.0009). CONCLUSIONS CD A/C+C/C and DPD1 C/C may be related to greater toxicity, and CD A/A may be a predictive marker of survival in capecitabine-treated CRC pts. Studies with a larger number of patients should be carried out to confirm these results. No significant financial relationships to disclose.

Cite this paper

@article{Ibeas2004CytidineD, title={Cytidine Deaminase (CD) and Dihydropyrimidine Dehydrogenase (DPD) single nucleotide polymorphisms (SNPs) in capecitabine-treated colorectal cancer (CRC).}, author={Rafael Ibeas and Mariano Monz{\'o} and Isabel Moreno and Raymundo Hernandez and Marc Campayo and Jun Pie and David Fuster and G Reyes Torres and Antonio Alcaide and Josep Jov{\'e}}, journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, year={2004}, volume={22 14_suppl}, pages={3662} }