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, Filippo Pietrantonio, Antonella Palazzo, Claudia Maggi, Francesca Ricchini, Filippo De Braud, Maria Di Bartolomeo

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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.

Original languageEnglish
Pages (from-to)1228-1237
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Volume78
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Fluorouracil
Meta-Analysis
Diarrhea
Incidence
irinotecan
Colorectal Neoplasms
oxaliplatin
Therapeutics
Randomized Controlled Trials
Capecitabine
MEDLINE
Population
Libraries
Stomach Neoplasms
Breast Neoplasms
Drug Therapy

Keywords

  • 5-fluorouracil
  • Breast cancer
  • Capecitabine
  • Colorectal cancer
  • Diarrhoea
  • Gastric cancer

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-fluorouracil : A meta-analysis of published trials. / Iacovelli, Roberto; Pietrantonio, Filippo; Palazzo, Antonella; Maggi, Claudia; Ricchini, Francesca; De Braud, Filippo; Di Bartolomeo, Maria.

In: British Journal of Clinical Pharmacology, Vol. 78, No. 6, 2014, p. 1228-1237.

Research output: Contribution to journalArticle

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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 = "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",
author = "Roberto Iacovelli and Filippo Pietrantonio and Antonella Palazzo and Claudia Maggi and Francesca Ricchini and {De Braud}, Filippo and {Di Bartolomeo}, Maria",
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T1 - Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-fluorouracil

T2 - A meta-analysis of published trials

AU - Iacovelli, Roberto

AU - Pietrantonio, Filippo

AU - Palazzo, Antonella

AU - Maggi, Claudia

AU - Ricchini, Francesca

AU - De Braud, Filippo

AU - Di Bartolomeo, Maria

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - 5-fluorouracil

KW - Breast cancer

KW - Capecitabine

KW - Colorectal cancer

KW - Diarrhoea

KW - Gastric cancer

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