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Oral versus intravenous fluoropyrimidines for colorectal cancer

Overview of attention for article published in Cochrane database of systematic reviews, July 2017
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83 Mendeley
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Title
Oral versus intravenous fluoropyrimidines for colorectal cancer
Published in
Cochrane database of systematic reviews, July 2017
DOI 10.1002/14651858.cd008398.pub2
Pubmed ID
Authors

Fiona Chionh, David Lau, Yvonne Yeung, Timothy Price, Niall Tebbutt

Abstract

Patients prefer oral to intravenous (IV) palliative chemotherapy, provided that oral therapy is not less effective. We compared the efficacy and safety of oral and IV fluoropyrimidines for treatment of colorectal cancer (CRC). To compare the effects of oral and IV fluoropyrimidine chemotherapy in patients treated with curative or palliative intent for CRC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), along with OVID MEDLINE, OVID Embase, and Web of Science databases, in June 2016. We also searched five clinical trials registers, several conference proceedings, and reference lists from study reports and systematic reviews. We contacted pharmaceutical companies to identify additional studies. We included randomised controlled trials (RCTs) comparing oral and IV fluoropyrimidine chemotherapy in patients treated with curative or palliative intent for CRC. Three review authors extracted data and assessed risk of bias independently. We assessed the seven domains in the Cochrane 'Risk of bias' tool and three additional domains: schedules of outcome assessment and/or follow-up; use of intention-to-treat analysis; and baseline comparability of treatment arms. We included nine RCTs (total of 10,918 participants) that examined treatment with curative intent for CRC with neoadjuvant and/or adjuvant chemotherapy. We included 35 RCTs (total of 12,592 participants) that examined treatment with palliative intent for inoperable advanced or metastatic CRC with chemotherapy (31 first-line studies, two second-line studies, and two studies of first- or second-line chemotherapy). All studies included male and female participants, and no studies included participants younger than 18 years of age. Patients treated with curative intent for CRC with neoadjuvant and/or adjuvant chemotherapy • Disease-free survival (DFS): DFS did not differ between participants treated with oral versus IV fluoropyrimidines (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.87 to 1.00; seven studies, 8903 participants; moderate-quality evidence).• Overall survival (OS): OS did not differ between participants treated with oral versus IV fluoropyrimidines (HR 0.92, 95% CI 0.84 to 1.00; seven studies, 8902 participants analysed; high-quality evidence).• Grade ≥ 3 adverse events (AEs): Participants treated with oral fluoropyrimidines experienced less grade ≥ 3 neutropenia/granulocytopenia (odds ratio (OR) 0.14, 95% CI 0.11 to 0.16; seven studies, 8087 participants; moderate-quality evidence), stomatitis (OR 0.21, 95% CI 0.14 to 0.30; five studies, 4212 participants; low-quality evidence), and any grade ≥ 3 AEs (OR 0.82, 95% CI 0.74 to 0.90; five studies, 7741 participants; low-quality evidence). There was more grade ≥ 3 hand foot syndrome (OR 4.59, 95% CI 2.97 to 7.10; five studies, 5731 participants; low-quality evidence) in patients treated with oral fluoropyrimidines. There were no differences between participants treated with oral versus IV fluoropyrimidines in occurrence of grade ≥ 3 diarrhoea (OR 1.12, 95% CI 0.99 to 1.25; nine studies, 9551 participants; very low-quality evidence), febrile neutropenia (OR 0.59, 95% CI 0.18 to 1.90; four studies, 2925 participants; low-quality evidence), vomiting (OR 1.05, 95% CI 0.83 to 1.34; eight studies, 9385 participants; low-quality evidence), nausea (OR 1.21, 95% CI 0.97 to 1.51; seven studies, 9233 participants; low-quality evidence), mucositis (OR 0.64, 95% CI 0.25 to 1.62; four studies, 2233 participants; very low-quality evidence), and hyperbilirubinaemia (OR 1.67, 95% CI 0.52 to 5.38; three studies, 2757 participants; very low-quality evidence). Patients treated with palliative intent for inoperable advanced or metastatic CRC with chemotherapy • Progression-free survival (PFS): Overall, PFS was inferior in participants treated with oral versus IV fluoropyrimidines (HR 1.06, 95% CI 1.02 to 1.11; 23 studies, 9927 participants; moderate-quality evidence). Whilst PFS was worse in participants treated with oral compared with IV fluoropyrimidines when UFT/Ftorafur or eniluracil with oral 5-fluorouracil (5-FU) was used, PFS did not differ between individuals treated with oral versus IV fluoropyrimidines when capecitabine, doxifluridine, or S-1 was used.• OS: Overall, OS did not differ between participants treated with oral versus IV fluoropyrimidines (HR 1.02, 95% CI 0.99 to 1.05; 29 studies, 12,079 participants; high-quality evidence). OS was inferior in participants treated with oral versus IV fluoropyrimidines when eniluracil with oral 5-fluorouracil (5-FU) was used.• Time to progression (TTP): TTP was inferior in participants treated with oral versus IV fluoropyrimidines (HR 1.07, 95% CI 1.01 to 1.14; six studies, 1970 participants; moderate-quality evidence).• Objective response rate (ORR): ORR did not differ between participants treated with oral versus IV fluoropyrimidines (OR 0.98, 95% CI 0.90 to 1.06; 32 studies, 11,115 participants; moderate-quality evidence).• Grade ≥ 3 AEs: Participants treated with oral fluoropyrimidines experienced less grade ≥ 3 neutropenia/granulocytopenia (OR 0.17, 95% CI 0.15 to 0.18; 29 studies, 11,794 participants; low-quality evidence), febrile neutropenia (OR 0.27, 95% CI 0.21 to 0.36; 19 studies, 9407 participants; moderate-quality evidence), stomatitis (OR 0.26, 95% CI 0.20 to 0.33; 21 studies, 8718 participants; low-quality evidence), mucositis (OR 0.17, 95% CI 0.12 to 0.24; 12 studies, 4962 participants; low-quality evidence), and any grade ≥ 3 AEs (OR 0.83, 95% CI 0.74 to 0.94; 14 studies, 5436 participants; low-quality evidence). There was more grade ≥ 3 diarrhoea (OR 1.66, 95% CI 1.50 to 1.84; 30 studies, 11,997 participants; low-quality evidence) and hand foot syndrome (OR 3.92, 95% CI 2.84 to 5.43; 18 studies, 6481 participants; moderate-quality evidence) in the oral fluoropyrimidine arm. There were no differences between oral and IV fluoropyrimidine arms in terms of grade ≥ 3 vomiting (OR 1.18, 95% CI 1.00 to 1.40; 23 studies, 9528 participants; low-quality evidence), nausea (OR 1.16, 95% CI 0.99 to 1.36; 25 studies, 9796 participants; low-quality evidence), and hyperbilirubinaemia (OR 1.62, 95% CI 0.99 to 2.64; nine studies, 2699 participants; low-quality evidence). Results of this review should provide confidence that treatment for CRC with most of the oral fluoropyrimidines commonly used in current clinical practice is similarly efficacious to treatment with IV fluoropyrimidines. Treatment with eniluracil with oral 5-FU was associated with inferior PFS and OS among participants treated with palliative intent for CRC, and eniluracil is no longer being developed. Oral and IV fluoropyrimidines have different patterns of side effects; future research may focus on determining the basis for these differences.

Twitter Demographics

The data shown below were collected from the profiles of 10 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 83 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 13 16%
Researcher 11 13%
Student > Master 11 13%
Other 7 8%
Student > Ph. D. Student 5 6%
Other 11 13%
Unknown 25 30%
Readers by discipline Count As %
Medicine and Dentistry 31 37%
Nursing and Health Professions 10 12%
Biochemistry, Genetics and Molecular Biology 5 6%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Economics, Econometrics and Finance 2 2%
Other 5 6%
Unknown 26 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2018.
All research outputs
#3,556,822
of 14,075,380 outputs
Outputs from Cochrane database of systematic reviews
#6,297
of 10,839 outputs
Outputs of similar age
#79,550
of 267,703 outputs
Outputs of similar age from Cochrane database of systematic reviews
#177
of 254 outputs
Altmetric has tracked 14,075,380 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 10,839 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.6. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,703 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 254 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.