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Meta-Analysis
. 2016 Feb 12;2(2):CD008593.
doi: 10.1002/14651858.CD008593.pub3.

Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer

Wahyu Wulaningsih  1 , Ardyan Wardhana, Johnathan Watkins, Naomi Yoshuantari, Dimitra Repana, Mieke Van Hemelrijck
Affiliations
Meta-Analysis

Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer

Wahyu Wulaningsih et al. Cochrane Database Syst Rev. .

Abstract

Background: Chemotherapy is the treatment of choice in patients with advanced or metastatic colorectal cancer (CRC) where surgical resection of metastases is not an option. Both irinotecan (IRI) and fluoropyrimidines are often included in first- or second- line chemotherapy treatment regimens in such patients. However, it is not clear whether combining these agents is superior to irinotecan alone.

Objectives: To compare the efficacy and safety of two chemotherapeutic regimens, irinotecan monotherapy or irinotecan in combination with fluoropyrimidines, for patients with advanced CRC when administered in the first or second-line settings.

Search methods: We searched the following electronic databases to identify randomized controlled trials: Cochrane Colorectal Cancer Group Specialised Register (January 13, 2016), Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library Issue 12, 2016), Ovid MEDLINE (1950 to January 13, 2016), Ovid EMBASE (1974 to January 13, 2016), registers of controlled trials in progress, references cited in relevant publications and conference proceedings in related fields (BioMed Central and Medscape's Conference). The key authors or investigators of all eligible studies, and professionals in the field were contacted when necessary. The search from January 2016 identified one eligible study, an ongoing trial currently presented as an abstract, to be considered in an update of this review.

Selection criteria: Randomized controlled trials (RCTs) investigating the efficacy and safety of IRI chemotherapy combined with fluoropyrimidine compared with IRI alone for the treatment of patients with advanced CRC, regardless of treatment line settings.

Data collection and analysis: Study eligibility and methodological quality were assessed independently by the two authors, and any disagreement was solved by a third author. The data collected from the studies were reviewed qualitatively and quantitatively using the Cochrane Collaboration statistical software RevMan 5.3.

Main results: Five studies were included in this review with a total of 1,726 patients. The top-up search resulted in an additional ongoing trial, the results of which have not been incorporated in this review. Among five included studies, no reduction in all-cause mortality was observed in the combination arm, with a summary hazard ratio (HR) of 0.91 (95% CI: 0.81-1.02). Longer progression-free survival was observed in those treated with the combination chemotherapy (HR: 0.68, 95% CI: 0.53-0.87), however, this result may have been driven by findings from the single first-line treatment setting study.The quality of evidence for overall survival was low and for progression-free survival was moderate, mainly due to study limitation from the lack of information on randomisation methods and allocation concealment.There were higher risks of toxicity outcomes grade 3 or 4 diarrhoea and grade 1 or 2 alopecia, and a lower risk of grade 3 or 4 neutropenia in controls compared to the invervention group. Evidence for toxicity has been assessed to be low to moderate quality.

Authors' conclusions: There was no overall survival benefit of the irinotecan and fluoropyrimidine treatment over irinotecan alone, thus both regimens remain reasonable options in treating patients with advanced or metastatic CRC. Given the low and moderate quality of the evidence, future studies with sufficient numbers of patients in each treatment arms are needed to clarify the benefit observed in progression-free survival with combination irinotecan and fluoropyrimidines.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

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Study flow diagram
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Funnel plot for comparisons of overall survival
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Overall survival.
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Progression‐free survival
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Response to treatment (CR + PR)
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Grade 3/4 diarrhea
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Grade 3/4 mucositis
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Grade 3/4 nausea
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Grade 3/4 vomiting
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Grade 3/4 neutropenia
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Febrile neutropenia
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Grade 1/2 alopecia
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Neuropathy
1.1
1.1. Analysis
Comparison 1 Overall Survival, Outcome 1 Overall survival.
1.2
1.2. Analysis
Comparison 1 Overall Survival, Outcome 2 Overall survival.
2.1
2.1. Analysis
Comparison 2 Progression‐Free Survival, Outcome 1 Progression‐free survival.
3.1
3.1. Analysis
Comparison 3 Response to Treatment, Outcome 1 Objective response (CR + PR).
4.1
4.1. Analysis
Comparison 4 Toxicity, Outcome 1 Grade 3/4 diarrhea.
4.2
4.2. Analysis
Comparison 4 Toxicity, Outcome 2 Grade 3/4 mucositis.
4.3
4.3. Analysis
Comparison 4 Toxicity, Outcome 3 Grade 3/4 nausea.
4.4
4.4. Analysis
Comparison 4 Toxicity, Outcome 4 Grade 3/4 vomiting.
4.5
4.5. Analysis
Comparison 4 Toxicity, Outcome 5 Grade 3/4 neutropenia.
4.6
4.6. Analysis
Comparison 4 Toxicity, Outcome 6 Febrile neutropenia.
4.7
4.7. Analysis
Comparison 4 Toxicity, Outcome 7 Grade 1/2 alopecia.
4.8
4.8. Analysis
Comparison 4 Toxicity, Outcome 8 Neuropathy.
4.9
4.9. Analysis
Comparison 4 Toxicity, Outcome 9 Grade 3/4 anemia.
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  • doi: 10.1002/14651858.CD008593.pub2

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References

References to studies included in this review

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