Background and importance Colorectal cancer (CRC) is one of the most prevalent neoplasms worldwide. Capecitabine (Xeloda), an oral prodrug of 5-fluorouracil, is one of the standard treatments for patients with advanced CRC (stages III-IV). In clinical practice, capecitabine response shows high interindividual variability. This variability may be due to the presence of polymorphisms in genes related to the bioactivation of capecitabine to fluorouracil (CES1, CES2, CDA, TYMP) that may alter drug bioavailability.
Aim and objectives To assess treatment response and evaluate the influence of genetic polymorphisms in CES1 (rs71647871, rs71647871), CES1P1 (rs rs7187684, rs11861118), CES2 (rs11075646), CDA (rs532545, rs602950, rs2072671), TYMP (rs11479) as predictive biomarkers in CRC patients treated with capecitabine.
Material and methods A prospective cohort study was carried out in CRC patients under adjuvant capecitabine treatment. DNA was extracted from buccal swabs. Genetic polymorphisms were determined by real-time polymerase chain reaction (PCR) with TaqMan probes. Treatment response was assessed using the RECIST criteria v1.1 for complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients were grouped intp response (CR+PR) and no response (SD+PD).
Results 53 CRC patients were included; 43.4% (23/53) were woman; mean age was 63±11 years; 54.72% (29/53) had family history of cancer; 84.62% (44/52) had adenocarcinoma, major cancer stage was IIIB 57.69% (30/52), the principal primary tumour location was rectum 37.74 (20/53) and main histological grade was G2 54.72% (29/53). Main treatment regimens were XELOX 58.49% (31/53) and capecitabine monotherapy 37.74% (20/53). 88.68% used capecitabine-based regimens as first line of treatment. Response could be evaluated in 50 patients. RECIST response was 76% CR (38/50), 4% SD (2/50) and 20% PD (10/50). Overall, 78% (39/50) patients responded to treatment. An association between tumour grade and response was observed (p=0.03), OR 2.71; 95% CI 1.82 to 189.39 for G1 vs G3 and OR 2.17; 95% CI 1.35 to 78.39 for G2 vs G3. No significant association was found between treatment response and the analysed polymorphisms (p>0.05).
Conclusion and relevance CRC patients with lower histological grades are associated with capecitabine-positive response. No significant association was found between response and genetic variants in CES1, CES2, CDA and TYMP.
Conflict of interest No conflict of interest
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