eflornithine and Adenoma studies

Eflornithine: An inhibitor of ORNITHINE DECARBOXYLASE, the rate limiting enzyme of the polyamine biosynthetic pathway.
eflornithine : A fluoroamino acid that is ornithine substituted by a difluoromethyl group at position 2.

Research Excerpts

Excerpt	Relevance	Reference
"Chemoprevention with the polyamine-inhibitory regimen difluoromethylornithine (DFMO) + sulindac markedly reduces risk of recurrent adenoma in colorectal adenoma patients."	9.16	Role of obesity in a randomized placebo-controlled trial of difluoromethylornithine (DFMO) + sulindac for the prevention of sporadic colorectal adenomas. ( Gerner, EW; Lin, BS; Madson, N; McLaren, CE; Meyskens, FL; Zell, JA, 2012)
" We evaluated the effect of baseline CV risk on adverse CV events in a phase III trial of difluoromethylornithine (DFMO) plus the NSAID sulindac versus placebo in preventing colorectal adenomas."	9.14	Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. ( Chen, WP; Gerner, EW; McLaren, CE; Meyskens, FL; Pelot, D; Zell, JA, 2009)
"The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas."	7.79	Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas. ( Gerner, EW; McLaren, CE; Meyskens, FL; Raj, KP; Rock, CL; Zell, JA; Zoumas-Morse, C, 2013)
" These COX-2 and ODC inhibitor drugs were not overtly toxic at the doses used when administered to mice after weaning."	5.31	Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. ( Cole, CE; Hawk, ET; Jacoby, RF; Kelloff, G; Lubet, RA; Newton, MA; Tutsch, K, 2000)
"Chemoprevention with the polyamine-inhibitory regimen difluoromethylornithine (DFMO) + sulindac markedly reduces risk of recurrent adenoma in colorectal adenoma patients."	5.16	Role of obesity in a randomized placebo-controlled trial of difluoromethylornithine (DFMO) + sulindac for the prevention of sporadic colorectal adenomas. ( Gerner, EW; Lin, BS; Madson, N; McLaren, CE; Meyskens, FL; Zell, JA, 2012)
" We evaluated the effect of baseline CV risk on adverse CV events in a phase III trial of difluoromethylornithine (DFMO) plus the NSAID sulindac versus placebo in preventing colorectal adenomas."	5.14	Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. ( Chen, WP; Gerner, EW; McLaren, CE; Meyskens, FL; Pelot, D; Zell, JA, 2009)
"The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas."	3.79	Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas. ( Gerner, EW; McLaren, CE; Meyskens, FL; Raj, KP; Rock, CL; Zell, JA; Zoumas-Morse, C, 2013)
" These COX-2 and ODC inhibitor drugs were not overtly toxic at the doses used when administered to mice after weaning."	1.31	Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. ( Cole, CE; Hawk, ET; Jacoby, RF; Kelloff, G; Lubet, RA; Newton, MA; Tutsch, K, 2000)

Research

Studies (18)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Adverse Events With a Grade of 3 and Above

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (5.56)	18.2507
2000's	11 (61.11)	29.6817
2010's	6 (33.33)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Zell, J	1
You, YN	1
Boughey, JC	1
Meyskens, FL	6
McLaren, CE	6
Pelot, D	2
Fujikawa-Brooks, S	1
Carpenter, PM	1
Hawk, E	1
Kelloff, G	2
Lawson, MJ	1
Kidao, J	1
McCracken, J	1
Albers, CG	1
Ahnen, DJ	1
Turgeon, DK	1
Goldschmid, S	1
Lance, P	1
Hagedorn, CH	1
Gillen, DL	1
Gerner, EW	8
Ignatenko, NA	1
Besselsen, DG	1
Stringer, DE	1
Blohm-Mangone, KA	1
Cui, H	1
Sporn, MB	1
Hong, WK	1
Zell, JA	5
Chen, WP	3
Thompson, PA	2
Wertheim, BC	1
LaFleur, BJ	1
Laukaitis, CM	1
Lin, BS	1
Madson, N	1
Raj, KP	1
Rock, CL	1
Zoumas-Morse, C	1
Gill, S	1
Sinicrope, FA	1
Tuma, R	1
Lehnert, T	1
Buhl, K	1
Ivankovic, S	1
Halberg, RB	1
Katzung, DS	1
Hoff, PD	1
Moser, AR	1
Cole, CE	2
Lubet, RA	3
Donehower, LA	1
Jacoby, RF	2
Dove, WF	1
Tutsch, K	1
Newton, MA	1
Hawk, ET	2
Krishnan, K	1
Ruffin, MT	1
Brenner, DE	1
Gunning, WT	1
Kramer, PM	1
Steele, VE	1
Pereira, MA	1
Umar, A	1
Viner, JL	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase III Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Combination of DFMO and Sulindac to Decrease the Rate of Recurrence of Adenomatous Polyps in the Colon[NCT00118365]	Phase 3	375 participants (Actual)	Interventional	1998-07-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"Participants reported at least 1 adverse event with a grade of 3 and above, regardless if the event is defined as serious per protocol or other.~Per protocol, not all grade 3 events are considered as serious events." (NCT00118365)
Timeframe: Up to 36 months

Baseline Putrescine by ODC Genotype

Intervention	participants (Number)
Arm I (Eflornithine and Sulindac)	46
Arm II (Placebo)	37

ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete. (NCT00118365)
Timeframe: Baseline

Baseline Spermidine by ODC Genotype

Intervention	nmol/mg protein (Median)
ODC1 AA/GA	0.47
ODC1 GG	0.56

Baseline Spermine by ODC Genotype

Intervention	nmol/mg protein (Median)
ODC1 AA/GA	1.99
ODC1 GG	2.17

Biomarker in Adenoma - Ki-67

Intervention	nmol/mg protein (Median)
ODC1 AA/GA	6.82
ODC1 GG	7.29

Estimated mean percent of cells staining postivie for the Ki-67 based on the GEE approach with adjustment for covariates (NCT00118365)
Timeframe: At the end of the study

Biomarker in Adenoma - p53

Intervention	percentage of cells that are positive (Mean)
Arm I (Eflornithine and Sulindac)	59.5
Arm II (Placebo)	63.9

"Estimated mean percent of cells staining postivie for p53 based on GEE approach with adjument for covariates.~Tumor protein p53, also known as p53, cellular tumor antigen p53, phosphoprotein p53, or tumor suppressor p53, is a protein that in humans is encoded by the TP53 gene." (NCT00118365)
Timeframe: At the end of the study

Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group

Intervention	percentage of cells that are positive (Mean)
Arm I (Eflornithine and Sulindac)	75.6
Arm II (Placebo)	70.3

At the End of the Study - Putrescine Response by ODC Genotype

Intervention	participants (Number)
DFMO + Sulindac - GG	7
DFMO + Sulindac - AA/GA	9
Placebo - GG	22
Placebo - AA/GA	18

"Putrescine responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) ≥ the threshold. Putrescine non-responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.~ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete." (NCT00118365)
Timeframe: At the end of the study

At the End of the Study - Spermidine Response by ODC Genotype

Intervention	participants (Number)
	Responder	Non-Responder
DFMO + Sulindac - AA/GA	21	19
DFMO + Sulindac - GG	26	32
Placebo - AA/GA	12	37
Placebo - GG	12	31

"Spermidine responder was defined as (tissue spermidine value at baseline - tissue spermidine value at the end of the study)/(tissue spermidine value at baseline) ≥ the threshold. Spermidine non-responder was defined as (tissue spermidine value at baseline - tissue spermidine value at the end of the study)/(tissue spermidine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.~ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete." (NCT00118365)
Timeframe: At the end of the study

At the End of the Study - Spermine Response by ODC Genotype

Intervention	participants (Number)
	Responder	Non-Responder
DFMO + Sulindac - AA/GA	12	28
DFMO + Sulindac - GG	25	32
Placebo - AA/GA	11	38
Placebo - GG	15	28

"Spermine responder was defined as (tissue spermine value at baseline - tissue spermine value at the end of the study)/(tissue spermine value at baseline) ≥ the threshold. Spermine non-responder was defined as (tissue spermine value at baseline - tissue spermine value at the end of the study)/(tissue spermine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.~ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete." (NCT00118365)
Timeframe: At the end of the study

Biomarker in Adenoma: Apoptosis

Intervention	participants (Number)
	Responder	Non-Responder
DFMO + Sulindac - AA/GA	7	33
DFMO + Sulindac - GG	7	51
Placebo - AA/GA	10	39
Placebo - GG	18	25

Apoptosis expression was assessed using cytoplasmic staining. The definitions for the category level for the Apoptosis are: 1. focal (less than 10% cells that are positively stained); 2. less than 50% cells are positively stained; 3. more than 50% cells are positively stained. (NCT00118365)
Timeframe: At the end of the study

Biomarker in Adenoma: Bcl-2

Intervention	adenoma (Number)
	A pattern equal to normal mucosa	1.focal (<10%)	2.cyto less than 50%	3.cyto more than 50%
Arm I (Eflornithine and Sulindac)	2	7	1	2
Arm II (Placebo)	4	20	23	13

bcl-2 is the anti-apoptotic protein BCL2 (NCT00118365)
Timeframe: At the end of the study, up to 3 years

Biomarker in Adenoma: CEA

Intervention	Adenoma (Number)
	A pattern equal to normal mucosa	1.<10% of the cells in the adenoma showed staining	2.10-50% cells showed staining	3.>50% cells showed staining	Insufficient tissue
Arm I (Eflornithine and Sulindac)	4	4	3	1	0
Arm II (Placebo)	17	25	14	8	2

carcino-embryonic antigen (CEA) is adenocarcinoma tissue marker that is expressed during adenoma formation. (NCT00118365)
Timeframe: At the end of the study

Biomarker in Adenoma: Sialyl-TN (B72.3)

Intervention	Adenoma (Number)
	A pattern equal to normal mucosa	1.<50% of cells showed staining	2.50-90% of cells showed staining	3.>90% of cells showed staining	Insufficient tissue
Arm I (Eflornithine and Sulindac)	1	5	6	0	0
Arm II (Placebo)	5	15	35	9	2

sialyl-Tn (B72.3) is adenocarcinoma tissue marker that is expressed during adenoma formation. (NCT00118365)
Timeframe: At the end of the study

Detection of Any Adenoma at the End of the Study

Intervention	Adenoma (Number)
	a pattern equal to normal mucosa	1.<10% of the cells in the adenoma showed staining	2.10-50% cells showed staining	3.>50% cells showed staining	Insufficient tissue
Arm I (Eflornithine and Sulindac)	3	7	2	0	0
Arm II (Placebo)	11	32	17	5	1

Detection of any adenoma at the end of the study. This analysis is based on the participants who had the end-of-study colonscopy procedure done. (NCT00118365)
Timeframe: Up to 36 months

Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment

Intervention	participants (Number)
	Yes	No
Arm I (Eflornithine and Sulindac)	17	121
Arm II (Placebo)	53	76

This analysis is based on the participants who had the end-of-study colonscopy procedure done and their baseline PGE2 values are available. The low PGE2 is defined as the values that are below the median PGE2 value in the analysis cohort. The high PGE2 is defined as the values that are above the median PGE2 value in the analysis cohort. (NCT00118365)
Timeframe: Up to 36 months

Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment

Intervention	participants (Number)
	Yes	No
Eflornithine and Sulindac + High PGE2 at Baseline	3	41
Eflornithine and Sulindac + Low PGE2 at Baseline	12	41
Placebo + High PGE2 at Baseline	21	32
Placebo + Low PGE2 at Baseline	19	23

The low is defined as the values that are below the median putrescine level in the analysis cohort. The high is defined as the values that are above the median putrescine level in the analysis cohort. (NCT00118365)
Timeframe: Up 36 months

Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment

Intervention	participants (Number)
	Yes	No
Eflornithine and Sulindac + High Putrescine at Baseline	10	56
Eflornithine and Sulindac + Low Putrescine at Baseline	7	63
Placebo + High Putrescine at Baseline	31	36
Placebo + Low Putrescine at Baseline	24	38

"The low is defined as the ratios that are below the median spermidine-to-spermine ratio in the analysis cohort. The high is defined as the ratios that are above the median spermidine-to-spermine ratio in the analysis cohort.~In the finalized datasaet, the total number of adnoma detected in the placebo group is 55. The descrepancy in the total number of adnoma detected in placebo group between Outcome Measure 1 and this oucome is due to the revolution of the datatset.~The analysis cohort is based on the participants whose data are available and complete." (NCT00118365)
Timeframe: Up 36 months

Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment

Intervention	participants (Number)
	Yes	No
Eflornithine and Sulindac + High Spd:Spm at Baseline	12	60
Eflornithine and Sulindac + Low Spd:Spm at Baseline	5	59
Placebo + High Spd:Spm at Baseline	24	37
Placebo + Low Spd:Spm at Baseline	31	37

PGE2 Responder = PGE2 values at 36-month are decreased by >=30% in PGE2 values from baseline PGE2 nonresponder = PGE2 values at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete. (NCT00118365)
Timeframe: Up to 36 months

Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment

Intervention	participants (Number)
	Yes	No
Eflornithine and Sulindac + PGE2 Nonresponders	8	27
Eflornithine and Sulindac + PGE2 Responders	1	10
Placebo + PGE2 Nonresponders	15	17
Placebo + PGE2 Responders	4	13

Putrescine responder = Putrescine values at 36-month are decreased by >=30% from baseline Putrescine nonresponder = Putrescine values at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete. (NCT00118365)
Timeframe: Up to 36 months

Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment

Intervention	participants (Number)
	Yes	No
Eflornithine and Sulindac + Putrescine Nonresponders	7	53
Eflornithine and Sulindac + Putrescine Responders	9	52
Placebo + Putrescine Nonresponders	28	44
Placebo + Putrescine Responders	22	24

Spermidine-to-spermine ratio responder = ratios at 36-month are decreased by >=30% from baseline Spermidine-to-spermine ratio nonresponder = ratios at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete. (NCT00118365)
Timeframe: Up to 36 months

Article	Year
DFMO: targeted risk reduction therapy for colorectal neoplasia. Best practice & research. Clinical gastroenterology, 2011, Volume: 25, Issue:4-5 Topics: Adenoma; Animals; Anticarcinogenic Agents; Chemoprevention; Colorectal Neoplasms; Eflornithine; Enzy	2011
Colorectal cancer prevention: is an ounce of prevention worth a pound of cure? Seminars in oncology, 2005, Volume: 32, Issue:1 Topics: Adenoma; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Aspirin; Calcium	2005
Chemoprevention for colorectal cancer. Critical reviews in oncology/hematology, 2000, Volume: 33, Issue:3 Topics: Adenoma; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Antioxidants; Ap	2000
The future of colon cancer prevention. Annals of the New York Academy of Sciences, 2001, Volume: 952 Topics: Adenocarcinoma; Adenoma; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents;	2001

Article	Year
Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer prevention research (Philadelphia, Pa.), 2008, Volume: 1, Issue:1 Topics: Adenoma; Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Colonoscopy; Color	2008
Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer prevention research (Philadelphia, Pa.), 2009, Volume: 2, Issue:3 Topics: Adenoma; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Antineoplast	2009
Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma. Gastroenterology, 2010, Volume: 139, Issue:3 Topics: Adenoma; Aged; Anticarcinogenic Agents; Biomarkers, Pharmacological; Biopsy; Colonoscopy; Colorectal	2010
Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients. Journal of the National Cancer Institute, 2010, Oct-06, Volume: 102, Issue:19 Topics: Adenoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Confounding Fac	2010
Role of obesity in a randomized placebo-controlled trial of difluoromethylornithine (DFMO) + sulindac for the prevention of sporadic colorectal adenomas. Cancer causes & control : CCC, 2012, Volume: 23, Issue:10 Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal	2012

Article	Year
PACES trial: Evaluating the effectiveness of eflornithine and sulindac in preventing colon adenomas. Bulletin of the American College of Surgeons, 2015, Volume: 100, Issue:8 Topics: Adenoma; Antineoplastic Agents; Clinical Trials as Topic; Colon; Colonic Neoplasms; Eflornithine; Hu	2015
Combination chemoprevention of intestinal carcinogenesis in a murine model of familial adenomatous polyposis. Nutrition and cancer, 2008, Volume: 60 Suppl 1 Topics: Adenoma; Adenomatous Polyposis Coli; Animals; Biogenic Polyamines; Celecoxib; Chemoprevention; Eflor	2008
Clinical prevention of recurrence of colorectal adenomas by the combination of difluoromethylornithine and sulindac: an important milestone. Cancer prevention research (Philadelphia, Pa.), 2008, Volume: 1, Issue:1 Topics: Adenoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colorectal Neopla	2008
Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas. British journal of cancer, 2013, Feb-19, Volume: 108, Issue:3 Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Clinical Tr	2013
Drugs to prevent colon cancer show promise, but hurdles remain for chemoprevention. Journal of the National Cancer Institute, 2008, Jun-04, Volume: 100, Issue:11 Topics: Adenoma; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Combined Chemotherapy Prot	2008
Inhibition of gastric tumorigenesis by alpha-difluoromethylornithine in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine. Journal of cancer research and clinical oncology, 1993, Volume: 119, Issue:10 Topics: Adenocarcinoma; Adenoma; Animals; Cell Transformation, Neoplastic; Duodenal Neoplasms; Eflornithine;	1993
Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers. Proceedings of the National Academy of Sciences of the United States of America, 2000, Mar-28, Volume: 97, Issue:7 Topics: Adenoma; Animals; Eflornithine; Female; Fibromatosis, Aggressive; Genes, APC; Genes, p53; Intestinal	2000
Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Cancer research, 2000, Apr-01, Volume: 60, Issue:7 Topics: Adenoma; Animals; Anticarcinogenic Agents; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhi	2000
Chemoprevention of vinyl carbamate-induced lung tumors in strain A mice. Experimental lung research, 2000, Volume: 26, Issue:8 Topics: Adenocarcinoma; Adenoma; Animals; Anticarcinogenic Agents; Carcinogens; Chemoprevention; Dexamethaso	2000

eflornithine and Adenoma