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Review
. 2014 Dec;78(6):1228-37.
doi: 10.1111/bcp.12449.

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

Roberto Iacovelli  1 , Filippo Pietrantonio, Antonella Palazzo, Claudia Maggi, Francesca Ricchini, Filippo de Braud, Maria Di Bartolomeo
Affiliations
Review

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

Roberto Iacovelli et al. Br J Clin Pharmacol. 2014 Dec.

Abstract

Aim: Capecitabine 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).

Methods: MEDLINE 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

Results: Twenty-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.

Conclusions: Treatment 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.

Keywords: 5-fluorouracil; breast cancer; capecitabine; colorectal cancer; diarrhoea; gastric cancer.

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Figures

Figure 1
Figure 1
PRISMA diagram; selection process for trials included in meta-analysis
Figure 2
Figure 2
Forest plot of relative risk (RR) of severe diarrhoea events associated with capecitabine in the overall population
Figure 3
Figure 3
Forest plot of relative risk (RR) of severe diarrhoea events associated with capecitabine in colorectal cancer patients treated with (A) oxaliplatin-based, (B) irinotecan-based combination of therapies or with (C) monotherapy
See this image and copyright information in PMC

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