ArticlePloS one2015
A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Eflornithine for chemoprevention in the high-risk population of colorectal cancer: a systematic review and meta-analysis with trial sequential analysis.Frontiers in oncology · 2023Pooled it
- Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.Cell reports. Medicine · 2023Trial
- Maintenance DFMO Increases Survival in High Risk Neuroblastoma.Scientific reports · 2018Trial
- Accelerating Pediatric Oncology Drug Development: Advances in Clinical Pharmacology, Trial Design, Non-Clinical Evidence, and Regulatory Science.Journal of clinical pharmacology · 2026Review
- Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review.American journal of medical genetics. Part A · 2026Review
- ARID1A deficiency-driven reprogramming of polyamine metabolism promotes endometrial cancer malignancy and immune escape.Cell death & disease · 2026Article
- Polyamines in Cancer: Mechanisms, Metabolic Targets, and Therapeutic Opportunities.Anti-cancer agents in medicinal chemistry · 2026Review
- ODC-Driven Polyamines Synthesis Sustains the Self-Renewal of Glioblastoma Stem Cells and Drives Tumor Aggressiveness.Cancer science · 2025Article
- High-dose DFMO alters protein translation in neuroblastoma.Neoplasia (New York, N.Y.) · 2025Article
- Repurposing With Purpose: Treatment of Bachmann-Bupp Syndrome With Eflornithine and Implications for Other Polyaminopathies.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Article
- Metabolic Imprint of Poliovirus on Glioblastoma Cells and Its Role in Virus Replication and Cytopathic Activity.International journal of molecular sciences · 2025Article
- Hydrogen Gas Attenuates Toxic Metabolites and Oxidative Stress-Mediated Signaling to Inhibit Neurodegeneration and Enhance Memory in Alzheimer's Disease Models.International journal of molecular sciences · 2025Article
- Design, Synthesis, and Biological Activity of Novel Ornithine Decarboxylase (ODC) Inhibitors.Journal of medicinal chemistry · 2025Article
- The polyamine transporter ATP13A3 mediates difluoromethylornithine-induced polyamine uptake in neuroblastoma.Molecular oncology · 2025Article
- AZIN1 level is increased in medulloblastoma and correlates with c-Myc activity and tumor phenotype.Journal of experimental & clinical cancer research : CR · 2025Article
- Polyamine Inhibition with DFMO: Shifting the Paradigm in Neuroblastoma Therapy.Journal of clinical medicine · 2025Review
- The RET inhibitor pralsetinib suppresses TMZ-resistant glioma growth by regulating spermine production.Frontiers in pharmacology · 2025Article
- Monitoring ODC activity and polyamines in Bachmann-Bupp syndrome patient biological samples.Methods in enzymology · 2025Article
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.Cell death and differentiation · 2024Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 16 institutions in 2 countries.
Funding
Abstract
backgroundNeuroblastoma (NB) is the most common cancer in infancy and most frequent cause of death from extracranial solid tumors in children. Ornithine decarboxylase (ODC) expression is an independent indicator of poor prognosis in NB patients. This study investigated safety, response, pharmacokinetics, genetic and metabolic factors associated with ODC in a clinical trial of the ODC inhibitor difluoromethylornithine (DFMO) ± etoposide for patients with relapsed or refractory NB. METHODS AND
findingsTwenty-one patients participated in a phase I study of daily oral DFMO alone for three weeks, followed by additional three-week cycles of DFMO plus daily oral etoposide. No dose limiting toxicities (DLTs) were identified in patients taking doses of DFMO between 500-1500 mg/m2 orally twice a day. DFMO pharmacokinetics, single nucleotide polymorphisms (SNPs) in the ODC gene and urinary levels of substrates for the tissue polyamine exporter were measured. Urinary polyamine levels varied among patients at baseline. Patients with the minor T-allele at rs2302616 of the ODC gene had higher baseline levels (p=0.02) of, and larger decreases in, total urinary polyamines during the first cycle of DFMO therapy (p=0.003) and had median progression free survival (PFS) that was over three times longer, compared to patients with the major G allele at this locus although this last result was not statistically significant (p=0.07). Six of 18 evaluable patients were progression free during the trial period with three patients continuing progression free at 663, 1559 and 1573 days after initiating treatment. Median progression-free survival was less among patients having increased urinary polyamines, especially diacetylspermine, although this result was not statistically significant (p=0.056).
conclusionsDFMO doses of 500-1500 mg/m2/day are safe and well tolerated in children with relapsed NB. Children with the minor T allele at rs2302616 of the ODC gene with relapsed or refractory NB had higher levels of urinary polyamine markers and responded better to therapy containing DFMO, compared to those with the major G allele at this locus. These findings suggest that this patient subset may display dependence on polyamines and be uniquely susceptible to therapies targeting this pathway.
trial registrationClinicaltrials.gov NCT#01059071.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.