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Indian Journal of Dermatology,... 2007
Review
Topics: Administration, Topical; Eflornithine; Enzyme Inhibitors; Hair Follicle; Hair Removal; Hirsutism; Humans; Ornithine Decarboxylase Inhibitors
PubMed: 17921631
DOI: 10.4103/0378-6323.35752 -
American Journal of Clinical Dermatology 2001Eflornithine is a specific, irreversible inhibitor of the enzyme ornithine decarboxylase which is thought to slow hair growth by inhibiting this enzyme in hair... (Review)
Review
Eflornithine is a specific, irreversible inhibitor of the enzyme ornithine decarboxylase which is thought to slow hair growth by inhibiting this enzyme in hair follicles. Percutaneous absorption of eflornithine in women with unwanted facial hair (hirsutism) was < 1% when the 15% cream was applied twice daily to a shaved 50 cm2 area of skin under the chin. In clinical studies in women with excessive, unwanted facial hair, eflornithine 15% cream was superior to placebo in reducing hair growth, as demonstrated by objective and subjective methods, after 2 to 8 weeks' treatment. After 24 weeks' treatment, 58% of eflornithine and 34% of placebo recipients had at least some improvement in facial hirsutism (for the purposes of this analysis all patients not assessed at week 24 were considered to be worse or to have no improvement). In addition, 32 versus 8% of patients were judged to be successfully treated (at least marked improvement). Hair growth returned to pretreatment rates within 8 weeks of stopping treatment. Use of a self-assessment questionnaire to assess the effect of study treatment on 6 aspects of patient well-being showed that eflornithine reduced the mean level of overall discomfort and bother by 33 versus 15% in placebo recipients. Adverse events mostly affected the skin. Only burning/stinging/tingling was markedly more common with eflornithine than with placebo.
Topics: Administration, Cutaneous; Chemistry, Pharmaceutical; Eflornithine; Face; Female; Hair Follicle; Hirsutism; Humans; Ornithine Decarboxylase Inhibitors; Safety; Skin Absorption; Treatment Outcome
PubMed: 11705097
DOI: 10.2165/00128071-200102030-00009 -
Journal of Clinical Oncology : Official... Jan 2024Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse...
PURPOSE
Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion of immunotherapy was investigated previously in a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free survival (EFS) and overall survival (OS) compared with historical rates in a phase III trial (Children Oncology Group ANBL0032; ClinicalTrials.gov identifier: NCT00026312). Using patient-level data from ANBL0032 as an external control, we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance.
PATIENTS AND METHODS
NMTRC003B (2012-2016) enrolled patients with HRNB (N = 141) after standard up-front or refractory/relapse treatment who received up to 2 years of continuous treatment with oral DFMO (750 ± 250 mg/m twice a day). ANBL0032 (2001-2015) enrolled patients with HRNB postconsolidation, 1,328 of whom were assigned to dinutuximab (ch.14.18) treatment. Selection rules identified 92 NMTRC003B patients who participated in (n = 87) or received up-front treatment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who could have been eligible for NMTRC003B after immunotherapy, but did not enroll (the NO-DFMO/control group). The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients. Kaplan-Meier and Cox regression compared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on 11 baseline demographic and disease characteristics with exact matching on , and additional sensitivity analyses.
RESULTS
DFMO after completion of immunotherapy was associated with improved EFS (hazard ratio [HR], 0.50 [95% CI, 0.29 to 0.84]; = .008) and OS (HR, 0.38 [95% CI, 0.19 to 0.76]; = .007). The results were confirmed with propensity score-matched cohorts and sensitivity analyses.
CONCLUSION
The externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.
Topics: Child; Humans; Eflornithine; Propensity Score; Neoplasm Recurrence, Local; Neuroblastoma; Recurrence; Disease-Free Survival
PubMed: 37883734
DOI: 10.1200/JCO.22.02875 -
CNS Oncology Apr 2018This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that... (Review)
Review
This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that irreversibly inhibits the enzyme ornithine decarboxylase. It covers the use of eflornithine, alone or in combination, to treat high-grade gliomas. In addition, we provide an update on overall survival from The University of Texas MD Anderson Cancer Center Community Clinical Oncology Program and Clinical Trials Data Office that demonstrates a meaningful benefit in overall survival for eflornithine as a single agent and in combination with nitrosourea-based therapies for anaplastic gliomas. We also provide a framework for understanding the basis and study design of the ongoing pivotal, registrational Phase III multicenter trial for recurrent/progressive anaplastic astrocytoma.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Eflornithine; Glioma; Humans
PubMed: 29378419
DOI: 10.2217/cns-2017-0031 -
Skin Therapy Letter Sep 2021Hair removal practices have evolved from adhering to social, cultural, and religious traditions to meeting aesthetic standards. Hair removal methods can be divided into... (Review)
Review
Hair removal practices have evolved from adhering to social, cultural, and religious traditions to meeting aesthetic standards. Hair removal methods can be divided into two categories: 1) depilation, which involves removing the hair shaft and includes shaving and chemical depilatories, and 2) epilation, which involves removing the hair shaft, follicle, and bulb, and includes plucking, threading, waxing, sugaring, lasers, intense pulsed light system, electrolysis, and photodynamic therapy. Furthermore, an eflornithine hydrochloride 13.9% cream (Vaniqa®, neither an epilatory or depilatory technique), has been US FDA- and Health Canada-approved to slow the rate of facial hair growth and to be used in combination with other hair removal methods. All methods are temporary except for electrolysis, and each technique has advantages and disadvantages in terms of efficacy and adverse events. Importantly, most studies examining the efficacy of hair removal techniques are limited to darker hair and fairer skin, and further research is required especially for those with light-colored hair.
Topics: Eflornithine; Face; Hair Removal; Humans; Lasers; Photochemotherapy
PubMed: 34524781
DOI: No ID Found -
The Medical Letter on Drugs and... May 2024
Topics: Humans; Neuroblastoma; Eflornithine; Antineoplastic Agents
PubMed: 38696315
DOI: 10.58347/tml.2024.1702f -
Parasitology Research Jun 2003Eflornithine is the only new molecule registered for the treatment of human African trypanosomiasis over the last 50 years. It is the drug used mainly as a back-up for... (Review)
Review
Eflornithine is the only new molecule registered for the treatment of human African trypanosomiasis over the last 50 years. It is the drug used mainly as a back-up for melarsoprol refractory Trypanosoma brucei gambiense cases. The most commonly used dosage regimen for the treatment of T. b. gambiensesleeping sickness consists of 100 mg kg(-1) body weight at intervals of 6 h for 14 days (150 mg kg(-1) body weight in children) of eflornithine given as short infusions. Its efficacy against Trypanosoma brucei rhodesiense is limited due to the innate lack of susceptibility of this parasite based on a higher ornithine decarboxylase turnover. Adverse drug reactions during eflornithine therapy are frequent and the characteristics are similar to other cytotoxic drugs for the treatment of cancer. Their occurrence and intensity increase with the duration of treatment and the severity of the general condition of the patient. Generally, adverse reactions to eflornithine are reversible after the end of treatment. They include convulsions (7%), gastrointestinal symptoms like nausea, vomiting and diarrhea (10%-39%), bone marrow toxicity leading to anemia, leucopenia and thrombocytopenia (25-50%), hearing impairment (5% in cancer patients) and alopecia (5-10%). The drug arrests embryonic development in mice, rats and rabbits but the extent of excretion into breast milk is unknown. The mean half-life is around 3-4 h and the volume of distribution in the range of 0.35 l kg(-1). Renal clearance is about 2 ml min kg(-1) (i.v.) and accounts for more than 80% of drug elimination. Bioavailability of an orally administered 10 mg kg(-1) dose was estimated at 54%. One of the major determinants of successful treatment seems to be the cerebrospinal fluid drug level reached during treatment, and it was shown that levels above 50 micro mol l(-1) must be reached to attain the consistent clearance of parasites. Based on its trypanostatic rather than trypanocidal mode of action, it is a rather slow-acting drug.
Topics: Animals; Eflornithine; Humans; Trypanocidal Agents; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 12811548
DOI: 10.1007/s00436-002-0766-5 -
PLoS Neglected Tropical Diseases Jul 2021The polyamine synthesis inhibitor eflornithine is a recommended treatment for the neglected tropical disease Gambian human African trypanosomiasis in late stage. This...
The polyamine synthesis inhibitor eflornithine is a recommended treatment for the neglected tropical disease Gambian human African trypanosomiasis in late stage. This parasitic disease, transmitted by the tsetse fly, is lethal unless treated. Eflornithine is administered by repeated intravenous infusions as a racemic mixture of L-eflornithine and D-eflornithine. The study compared the in vitro antitrypanosomal activity of the two enantiomers with the racemic mixture against three Trypanosoma brucei gambiense strains. Antitrypanosomal in vitro activity at varying drug concentrations was analysed by non-linear mixed effects modelling. For all three strains, L-eflornithine was more potent than D-eflornithine. Estimated 50% inhibitory concentrations of the three strains combined were 9.1 μM (95% confidence interval [8.1; 10]), 5.5 μM [4.5; 6.6], and 50 μM [42; 57] for racemic eflornithine, L-eflornithine and D-eflornithine, respectively. The higher in vitro potency of L-eflornithine warrants further studies to assess its potential for improving the treatment of late-stage Gambian human African trypanosomiasis.
Topics: Eflornithine; Humans; Trypanocidal Agents; Trypanosoma brucei gambiense
PubMed: 34252098
DOI: 10.1371/journal.pntd.0009583 -
American Journal of Health-system... Dec 2001
Topics: Depression, Chemical; Drug Costs; Drug Interactions; Eflornithine; Hair; Hirsutism; Humans
PubMed: 11763800
DOI: 10.1093/ajhp/58.23.2244 -
The New England Journal of Medicine Sep 2020The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown.
METHODS
We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease.
RESULTS
A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups.
CONCLUSIONS
In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.).
Topics: Adenomatous Polyposis Coli; Adult; Disease Progression; Drug Therapy, Combination; Eflornithine; Female; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Sulindac; Treatment Outcome
PubMed: 32905675
DOI: 10.1056/NEJMoa1916063