eflornithine and Local Neoplasm Recurrence 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
"This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas."	9.07	Treatment of recurrent gliomas with eflornithine. ( Gleason, MJ; Ictech, S; Levin, VA; Malec, M; Prados, MD; Yung, WK, 1992)
"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)
"A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos."	5.13	Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. ( Chen, WP; Fujikawa-Brooks, S; Gerner, EW; Gillen, DL; McLaren, CE; Meyskens, FL; Pelot, D, 2008)
"This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas."	5.07	Treatment of recurrent gliomas with eflornithine. ( Gleason, MJ; Ictech, S; Levin, VA; Malec, M; Prados, MD; Yung, WK, 1992)
"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)
" Experiments were carried out on the trastuzumab-resistant human epidermal growth factor receptor 2-overexpressing breast cancer cell line JIMT-1 to unravel the chemotherapeutic effects of the polyamine analogue [1N,12N]bis(ethyl)-cis-6,7-dehydrospermine (PG11047) and of the polyamine biosynthetic inhibitor 2-difluoromethylornithine (DFMO) on the CD44+CD24- CSC population."	3.76	Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047. ( Cirenajwis, H; Hegardt, C; Honeth, G; Marton, LJ; Oredsson, SM; Smiljanic, S, 2010)
"Two patients died of bladder cancer at 2 and 4 years after randomization, both in the difluoromethylornithine arm."	2.72	Randomized prospective phase III trial of difluoromethylornithine vs placebo in preventing recurrence of completely resected low risk superficial bladder cancer. ( Kim, D; Kim, KM; Messing, E; Parnes, H; Saltzstein, D; Schultz, M; Sharkey, F; Wilding, G, 2006)
"Patients with resected superficial bladder cancers were studied."	2.68	Toxicity evaluation of difluoromethylornithine: doses for chemoprevention trials. ( Loprinzi, CL; Love, RR; Messing, EM; Morton, RF; Novotny, P; O'Fallon, JR; Poon, MA; Quella, SK; Trump, DL, 1996)

Research

Studies (18)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Area Under the Plasma Concentration Versus Time Curve (AUC)

Timeframe	Studies, this research(%)	All Research%
pre-1990	3 (16.67)	18.7374
1990's	5 (27.78)	18.2507
2000's	5 (27.78)	29.6817
2010's	4 (22.22)	24.3611
2020's	1 (5.56)	2.80

Authors	Studies
Batth, IS	1
Dao, L	1
Satelli, A	1
Mitra, A	1
Yi, S	1
Noh, H	1
Li, H	1
Brownlee, Z	1
Zhou, S	1
Bond, J	1
Wang, J	1
Gill, J	1
Sholler, GS	1
Li, S	1
Sporn, MB	1
Hong, WK	1
McLaren, CE	2
Fujikawa-Brooks, S	1
Chen, WP	1
Gillen, DL	1
Pelot, D	1
Gerner, EW	4
Meyskens, FL	2
Cirenajwis, H	1
Smiljanic, S	1
Honeth, G	1
Hegardt, C	1
Marton, LJ	1
Oredsson, SM	1
Laukaitis, CM	1
Rial, NS	1
Zell, JA	2
Cohen, AM	1
Raj, KP	1
Rock, CL	1
Zoumas-Morse, C	1
Manni, A	1
Washington, S	1
Craig, L	1
Cloud, M	1
Griffith, JW	1
Verderame, MF	1
Texter, LJ	1
Mauger, D	1
Demers, LM	1
Harms, JF	1
Welch, DR	1
Messing, E	1
Kim, KM	1
Sharkey, F	1
Schultz, M	1
Parnes, H	1
Kim, D	1
Saltzstein, D	1
Wilding, G	1
Tuma, R	1
Loprinzi, CL	2
Messing, EM	2
O'Fallon, JR	2
Poon, MA	1
Love, RR	1
Quella, SK	1
Trump, DL	1
Morton, RF	1
Novotny, P	1
Buckner, JC	1
Burch, PA	1
Cascino, TL	1
Scheithauer, BW	1
Hess, KR	1
Wong, ET	1
Jaeckle, KA	1
Kyritsis, AP	1
Levin, VA	4
Prados, MD	3
Yung, WK	2
Gleason, MJ	1
Ictech, S	1
Malec, M	1
Prados, M	1
Rodriguez, L	1
Chamberlain, M	1
Silver, P	2
Levin, V	1
Chamberlain, MC	1
Choucair, AK	1
Berger, MS	1
Seager, M	1
Gutin, PH	1
Davis, RL	1
Wilson, CB	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission[NCT02395666]	Phase 2	140 participants (Actual)	Interventional	2015-03-05	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"Pharmacokinetic assay AUC(0-6 hr)/D~Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days" (NCT02395666)
Timeframe: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Intervention	hr*ng/mL (Mean)
Study Subjects Consented to PK Collection	47024

To continue to determine the safety and tolerability of DFMO as a single agent and in pediatric and young adult patients with high risk neuroblastoma that is in remission. (NCT02395666)
Timeframe: 2 years

Number of Participants With Event Free Survival (EFS) During Study.

Intervention	Participants (Count of Participants)
DFMO Twice Daily	57

To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS) (NCT02395666)
Timeframe: 2 Years

Peak Plasma Concentration (Cmax)

Intervention	percentage of subjects without an event (Mean)
Stratum 1	84
Stratum 2	51

"Pharmacokinetic assay Cmax/D~Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days." (NCT02395666)
Timeframe: Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days

Percentage of Participants With Overall Survival (OS)

Intervention	ng/mL (Mean)
Study Subjects Consented to PK Collection	11958

To evaluate the preventative activity of DFMO as a single agent in patients with neuroblastoma who are in remission based on: Overall Survival (OS) (NCT02395666)
Timeframe: 2 Years

Test the Association of Survival With ODC1 Genotype

Intervention	percentage of subjects without an event (Mean)
Stratum 1	97
Stratum 2	84

"Tests (p-value) of the association of survival with ODC1 single nucleotide polymorphism rs2302616 genotype.~Blood: microRNA analysis as predictor of DFMO effect, ornithine decarboxylase (ODC) single nucleotide polymorphism (SNP) analysis in DNA isolated from nucleated cells" (NCT02395666)
Timeframe: 2 years

Time to Reach Peak Plasma Concentration (Tmax)

Intervention	p-value (Number)
GG, GT, TT	0.96
GG or GT, TT	0.58
GG, GT or TT	0.67

"Pharmacokinetic assay- tmax, hr~Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days" (NCT02395666)
Timeframe: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days

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
Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer. Expert review of gastroenterology & hepatology, 2012, Volume: 6, Issue:4 Topics: Adenomatous Polyposis Coli; Antineoplastic Agents; Chemoprevention; Clinical Trials as Topic; Colono	2012
A prospective clinical trial of difluoromethylornithine (DFMO) in patients with resected superficial bladder cancer. Journal of cellular biochemistry. Supplement, 1992, Volume: 16I Topics: Clinical Trials as Topic; Eflornithine; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; N	1992
Chemotherapy of primary brain tumors. Neurologic clinics, 1985, Volume: 3, Issue:4 Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Brain Stem; Child; Efl	1985

Article	Year
Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. Cancer prevention research (Philadelphia, Pa.), 2008, Volume: 1, Issue:7 Topics: Adenomatous Polyps; Antineoplastic Combined Chemotherapy Protocols; Audiometry, Pure-Tone; Colonic N	2008
Randomized prospective phase III trial of difluoromethylornithine vs placebo in preventing recurrence of completely resected low risk superficial bladder cancer. The Journal of urology, 2006, Volume: 176, Issue:2 Topics: Aged; Antineoplastic Agents; Carcinoma, Transitional Cell; Double-Blind Method; Eflornithine; Female	2006
Toxicity evaluation of difluoromethylornithine: doses for chemoprevention trials. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1996, Volume: 5, Issue:5 Topics: Antineoplastic Agents; Carcinoma, Transitional Cell; Chemoprevention; Dose-Response Relationship, Dr	1996
Phase II trial of recombinant interferon-alpha-2a and eflornithine in patients with recurrent glioma. Journal of neuro-oncology, 1998, Volume: 36, Issue:1 Topics: Adult; Aged; Disease Progression; Drug Therapy, Combination; Eflornithine; Female; Glioma; Humans; I	1998
Response and progression in recurrent malignant glioma. Neuro-oncology, 1999, Volume: 1, Issue:4 Topics: Actuarial Analysis; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Combine	1999
Treatment of recurrent gliomas with eflornithine. Journal of the National Cancer Institute, 1992, Sep-16, Volume: 84, Issue:18 Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Child, Preschool; Eflornithine; Female; Glioblastom	1992

Article	Year
Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. International journal of cancer, 2020, 12-15, Volume: 147, Issue:12 Topics: Biomarkers, Tumor; Cell Line, Tumor; Clinical Trials, Phase II as Topic; Early Detection of Cancer;	2020
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
Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047. Anti-cancer drugs, 2010, Volume: 21, Issue:10 Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms;	2010
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
Effects of alpha-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. Clinical & experimental metastasis, 2003, Volume: 20, Issue:4 Topics: Animals; Eflornithine; Enzyme Inhibitors; Female; Green Fluorescent Proteins; Humans; Luminescent Pr	2003
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
Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine. Neurosurgery, 1989, Volume: 24, Issue:6 Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Carmustine; Combined M	1989
Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors. Cancer treatment reports, 1987, Volume: 71, Issue:5 Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Drug Eval	1987

eflornithine and Local Neoplasm Recurrence