Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis

C. Y. Hsu, C. Y. Chen, Y. M. Lin, K. W. Tam

Research output: Contribution to journalReview article

Abstract

Aim: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. Method: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. Results: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference −0.06, 95% CI −0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55–1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. Conclusion: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

Original languageEnglish
JournalColorectal Disease
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Leucovorin
Meta-Analysis
Colorectal Neoplasms
Safety
Survival
Neoplasms
PubMed
Fluorouracil
Diarrhea
Therapeutics
Randomized Controlled Trials
Retrospective Studies
Databases

Keywords

  • 5-fluorouracil
  • colorectal cancer
  • dosage
  • leucovorin
  • shortage

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer : systematic review and meta-analysis. / Hsu, C. Y.; Chen, C. Y.; Lin, Y. M.; Tam, K. W.

In: Colorectal Disease, 01.01.2019.

Research output: Contribution to journalReview article

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abstract = "Aim: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. Method: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. Results: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference −0.06, 95{\%} CI −0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95{\%} CI 0.55–1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. Conclusion: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.",
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