Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5‐fluorouracil: a meta‐analysis of published trials

Abstract

AIMCapecitabine is an oral fluoropyrimidine that can effectively replace infusional 5-fluorouracil (5-FU) for treatment of colorectal, gastric and breast cancer. This study aims to analyze the incidence and the relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-FU in randomized clinical trials (RCTs). METHODSMEDLINE and Cochrane Library were reviewed for RCTs that compared capecitabine with 5-FU for treatment of solid malignancies. The incidence and relative risk (RR) of grade 3/4 diarrhoea were estimated for each arm in the overall population and in colorectal cancer (CRC) patients RESULTSTwenty-three studies and 15 761 patients were included. Among these 8303 and 7458 patients received capecitabine or 5-FU based therapies, respectively. In the overall populations severe diarrhoea was reported in 16.6% (95% CI 15.8, 17.4) and in 12.7% (95% CI 11.9, 13.4) of patients treated with capecitabine or 5-FU-based therapies, respectively. The RR was 1.39 (95% CI 1.14, 1.69, P = 0.0010). In 14 899 CRC patients, the incidence of severe diarrhoea was 17.0% (95% CI 16.2, 17.9) and 12.9% (95% CI 12.1, 13.7), respectively, with a RR of 1.46 (95% CI 1.18, 1.81, P < 0.0001). In CRC patients treated with combined chemotherapy, the RR was 1.40 (95% CI 1.07, 1.82; P = 0.01) for patients receiving oxaliplatin and 2.35 (95% CI 1.76, 3.13; P < 0.0001) for patients receiving irinotecan. CONCLUSIONSTreatment with capecitabine is characterized by an increased risk of severe diarrhoea, mainly in patients affected by CRC and treated with polichemotherapy. Combination treatment with irinotecan doubles the risk over 5-FU.

Capecitabine-Associated Terminal Ileitis

“…The diarrhea usually starts at the end of the second or in the third week, is mostly mild, recovers after a few days with sometimes a necessity of treatment with anti-motility agents such as loperamide. Grade 3–4 diarrhea occurs in 11.4% of patients treated with capecitabine monotherapy [ 1 ]. In contrast, in patients with a DPD deficiency the diarrhea starts often within the first week and is life threatening [ 2 ].…”

“…Oxaliplatin can also cause diarrhea but typically starts early after administration within 3–4 days and resolves after 1–2 days without any intervention. In patients treated with the combination of capecitabine and oxaliplatin, grade 3–4 diarrhea occurs in approximately 18% of cases [ 1 , 3 ].…”

Contribution of equilibrative nucleoside transporter(s) to intestinal basolateral and apical transports of anticancer trifluridine

“…In the present study, the mechanisms involved in the transcellular transport of FTD in the intestines were investigated using ENTexpressing Xenopus oocytes and HIEC monolayers in order to clarify its relationships with: (1) the sufficient membrane permeability of FTD to achieve relatively high absorption (~60%) in humans (Lee et al, 2016) despite its hydrophilic characteristics (log P = −0.452, pH 7), and (2) the lower incidence of intestinal toxicity of FTD (3%) (Mayer et al, 2015) in patients administered TAS-102 than in those given other chemotherapeutic agents such as capecitabine (17.0%), 5-FU (12.9%) and irinotecan (15%) (Iacovelli et al, 2014;Negoro et al, 2003).…”

“…Clinical trials revealed that the frequency of severe diarrhea caused by TAS‐102 (diarrhea of grade 3 or higher in 3% of the 533 patients who received TAS‐102 (Mayer et al, ) was lower than that by other chemotherapeutic agents such as capecitabine (17.0%), 5‐fluorouracil (12.9%) and irinotecan (15%) (Iacovelli et al, ; Negoro et al, ). These findings indicate that ENTs play a significant role in the basolateral efflux of FTD, which ameliorates the gastrointestinal toxicity of FTD by reducing the intracellular accumulation of FTD in the intestines.…”

Who Can Perform Adjuvant Chemotherapy Treatment for Gastric Cancer? A Multicenter Retrospective Overview of the Current Status in Korea

“…Diarrhea occurring during AC may be due to side effects of chemotherapy or it may be a symptom of dumping syndrome shortly after surgery [ 16 17 ]. It is important to know whether diarrhea persists after stopping the chemotherapy or after eating a large quantity of food or carbohydrates.…”