Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://gr.elmerpub.com

Review

Volume 18, Number 3, June 2025, pages 93-100

Eflornithine for the Chemoprevention of Luminal Gastrointestinal Neoplasms: A Systematic Review

**Table 1.** General Characteristics of the Included Studies
Study	Year	Risk of bias	Population	Design and follow-up	Study Arms (N)	Endpoint(s)	Conclusion
AB: attrition bias; CRC: colorectal cancer; CXB: celecoxib; DFMO: eflornithine; FAP: familial adenomatous polyposis; GI: gastrointestinal; GPMC: gastric premalignant condition; PB: publication bias; SB: selection bias.
Burke [21]	2020	“Low” SB “Low” PB “Low” AB	Adults aged 18 years or older who had clinical FAP and pathogenic variants of APC.	Randomly assigned in a 1:1:1 ratio, up to 24 months. To prevent CRC	DFMO 750 mg and sulindac 150 mg (N = 56) vs. DFMO 750 mg + placebo (N = 57) vs. sulindac 150 mg + placebo (N = 58).	Assessed in a time-to-event analysis, was disease progression.	HR for disease progression of 0.30 (95% CI, 0.30 - 1.32) DFMO + sulindac vs. sulindac and 0.20 (95% CI, 0.03 - 1.32) DFMO + sulindac vs. DFMO.
Lynch [22]	2016	“Low” SB “Low” PB “Low” AB	Adults aged 18 - 65 years who had clinical diagnosis of familial adenomatosis.	Randomized phase II trial To prevent CRC 6 months.	DFMO 0.5 g/m²/day rounded down to the nearest 250 mg dose + CXB 400 mg/day (N = 57) vs. CXB + placebo (N = 55).	Percentage change in adenoma count per field. Adenoma burden determined by adenoma diameter and video review of colorectum.	DFMO plus CXB yielded moderate synergy and video-based improvement. No significant difference in adenoma count.
Meyskens [23]	2008	“Low” SB “Low” PB “Low” AB	Adults aged 40 - 80 years with a history of ≥ 1 resected adenoma of at least 3 mm within 5 years before study entry.	Randomized, double-blinded placebo-controlled trial to test the reduction in the recurrences of colorectal adenomas. To prevent CRC Up to 3 years.	DFMO 500 mg + sulindac 150 mg/day (N = 191) vs. DFMO placebo + sulindac placebo (N = 184).	Adenoma burden and the total size and number of adenomas in the colon and rectum.	DFMO, when combined with sulindac, reduces risk of recurrent adenomas in patients with non-familial adenomas by about 70%.
Balaguer [24]	2022	“Low” SB “Low” PB “Low” AB	Adults with FAP.	Randomized, double-blinded placebo-controlled trial to evaluate the impact of DFMO-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with FAP.	DFMO (750 mg) once daily (N = 51) vs. sulindac (150 mg) once daily (N = 53) vs. DFMO (750 mg) + sulindac (150 mg) once daily (N = 54) for up to 48 months.	Time to first disease progression in the lower GI tract.	DFMO-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower GI tract surgery in patients with FAP.
Sinicrope [25]	2019	“Low” SB “Low” PB “Low” AB	Adults aged 46 to 83 years who had current or prior advanced colorectal adenomas.	Randomized, double-blinded, and placebo-controlled trial; taken continuously for 1 year. To prevent CRC	DFMO 500 mg/day + aspirin 325 mg/day (N = 43) vs. DFMO placebo + aspirin placebo (N = 44).	Compare adenoma number in at 1-year follow-up.	Compared to placebo, in a high-risk patient population, DFMO in addition to aspirin did not reduce adenoma recurrence in the colon or rectum at 1 year, but it did show lower risk of aberrant cryptic foci in the rectum.
Morgan [26]	2024	“Low” SB “Low” PB “Low” AB	Patients with GPMC from rural Honduras and Puerto Rico, aged 30 - 60 years, with high prevalence of H. pylori infection.	Randomized controlled trial; follow-up duration of 24 months.	DFMO vs. placebo.	Tolerability, safety, changes in Correa histopathology score, and DNA damage (%pH2AX positive cells).	DFMO treatment was safe and well tolerated in GPMC patients in Latin America. DFMO reduced long-term DNA damage in patients after completing treatment.

Table 1. General Characteristics of the Included Studies

Study

Year

Risk of bias

Population

Design and follow-up

Study Arms (N)

Endpoint(s)

Conclusion

AB: attrition bias; CRC: colorectal cancer; CXB: celecoxib; DFMO: eflornithine; FAP: familial adenomatous polyposis; GI: gastrointestinal; GPMC: gastric premalignant condition; PB: publication bias; SB: selection bias.

Burke [21]

2020

“Low” SB
“Low” PB
“Low” AB

Adults aged 18 years or older who had clinical FAP and pathogenic variants of APC.

Randomly assigned in a 1:1:1 ratio, up to 24 months.
To prevent CRC

DFMO 750 mg and sulindac 150 mg (N = 56) vs. DFMO 750 mg + placebo (N = 57) vs. sulindac 150 mg + placebo (N = 58).

Assessed in a time-to-event analysis, was disease progression.

HR for disease progression of 0.30 (95% CI, 0.30 - 1.32) DFMO + sulindac vs. sulindac and 0.20 (95% CI, 0.03 - 1.32) DFMO + sulindac vs. DFMO.

Lynch [22]

2016

“Low” SB
“Low” PB
“Low” AB

Adults aged 18 - 65 years who had clinical diagnosis of familial adenomatosis.

Randomized phase II trial
To prevent CRC
6 months.

DFMO 0.5 g/m²/day rounded down to the nearest 250 mg dose + CXB 400 mg/day (N = 57) vs. CXB + placebo (N = 55).

Percentage change in adenoma count per field. Adenoma burden determined by adenoma diameter and video review of colorectum.

DFMO plus CXB yielded moderate synergy and video-based improvement. No significant difference in adenoma count.

Meyskens [23]

2008

“Low” SB
“Low” PB
“Low” AB

Adults aged 40 - 80 years with a history of ≥ 1 resected adenoma of at least 3 mm within 5 years before study entry.

Randomized, double-blinded placebo-controlled trial to test the reduction in the recurrences of colorectal adenomas.
To prevent CRC
Up to 3 years.

DFMO 500 mg + sulindac 150 mg/day (N = 191) vs. DFMO placebo + sulindac placebo (N = 184).

Adenoma burden and the total size and number of adenomas in the colon and rectum.

DFMO, when combined with sulindac, reduces risk of recurrent adenomas in patients with non-familial adenomas by about 70%.

Balaguer [24]

2022

“Low” SB
“Low” PB
“Low” AB

Adults with FAP.

Randomized, double-blinded placebo-controlled trial to evaluate the impact of DFMO-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with FAP.

DFMO (750 mg) once daily (N = 51) vs. sulindac (150 mg) once daily (N = 53) vs. DFMO (750 mg) + sulindac (150 mg) once daily (N = 54) for up to 48 months.

Time to first disease progression in the lower GI tract.

DFMO-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower GI tract surgery in patients with FAP.

Sinicrope [25]

2019

“Low” SB
“Low” PB
“Low” AB

Adults aged 46 to 83 years who had current or prior advanced colorectal adenomas.

Randomized, double-blinded, and placebo-controlled trial; taken continuously for 1 year.
To prevent CRC

DFMO 500 mg/day + aspirin 325 mg/day (N = 43) vs. DFMO placebo + aspirin placebo (N = 44).

Compare adenoma number in at 1-year follow-up.

Compared to placebo, in a high-risk patient population, DFMO in addition to aspirin did not reduce adenoma recurrence in the colon or rectum at 1 year, but it did show lower risk of aberrant cryptic foci in the rectum.

Morgan [26]

2024

“Low” SB
“Low” PB
“Low” AB

Patients with GPMC from rural Honduras and Puerto Rico, aged 30 - 60 years, with high prevalence of H. pylori infection.

Randomized controlled trial; follow-up duration of 24 months.

DFMO vs. placebo.

Tolerability, safety, changes in Correa histopathology score, and DNA damage (%pH2AX positive cells).

DFMO treatment was safe and well tolerated in GPMC patients in Latin America. DFMO reduced long-term DNA damage in patients after completing treatment.