title: 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: OBJECTIVE
  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.
authors: Department of Meical Oncology, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy; PhD Program, Department of Radiology Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy.
authors: Roberto
authors: R
authors: Iacovelli
authors: Filippo
authors: F
authors: Pietrantonio
authors: Antonella
authors: A
authors: Palazzo
authors: Claudia
authors: C
authors: Maggi
authors: Francesca
authors: F
authors: Ricchini
authors: Filippo
authors: F
authors: de Braud
authors: Maria
authors: M
authors: Di Bartolomeo
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced*; D005472:Fluorouracil / Q000009:adverse effects* / Q000031:analogs & derivatives*; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
keywords: 5-fluorouracil; breast cancer; capecitabine; colorectal cancer; diarrhoea; gastric cancer