Eflornithine for neuroblastoma

Background:
Eflornithine, also known as difluoromethylornithine (DFMO), was originally registered as a treatment for African sleeping sickness (trypanosomiasis). It was later approved as a topical treatment to slow hair growth in people with hirsutism, under the brand name Vaniqa (no longer registered). It has now been approved as an oral maintenance therapy to reduce the risk of relapse in patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy.

Neuroblastoma is a malignancy of the autonomic nervous system that is responsible for about 15% of all cancer-related deaths in children. It is less common in adolescents and adults.¹ HRNB is neuroblastoma with a high risk of poor outcomes based on imaging stage, age, chromosomal abnormalities and pathology.¹ Treatment modalities for HRNB include intensive chemotherapy, surgery, radiation therapy, autologous stem cell transplantation and immunotherapy.^1-3 More than 50% of patients with HRNB will relapse despite intensive multimodality therapy.⁴

Mechanism of action:
Eflornithine irreversibly inhibits ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. Polyamines are small organic molecules that regulate cell growth and differentiation and control multiple oncogenes.^3,5 By blocking these pathways, eflornithine suppresses the growth of neuroblastoma tumours.¹

Clinical trials:
The efficacy of eflornithine was demonstrated in an externally controlled trial comparison, in which a multicentre, open label, non-randomised trial was prospectively designed to compare outcomes against a prior study where patients did not receive eflornithine maintenance therapy.^5,6 The comparative analysis included matched patients from both studies (90 and 270 patients respectively) who were less than 21 years of age with histologic verification of HRNB and at least a partial response to previous multimodality treatment. Median age at diagnosis was 3 years (range 0.1 to 20.1). Most patients (86%) had stage 4 disease, and MYCN gene amplification was observed in 44% of tumours. In the prospective study, patients received maintenance therapy with oral eflornithine 500 mg to 1000 mg/m² twice a day for up to 2 years. Patients were followed for up to 7 years. In the analysis of matched patients, the event-free survival hazard ratio (HR) was 0.48 (95% confidence interval [CI] 0.27 to 0.85) and overall survival HR was 0.32 (95% CI 0.15 to 0.70) favouring eflornithine-treated patients. Four-year overall survival was 96% versus 84% in the eflornithine and no-eflornithine groups. Given the uncertainty associated with the externally controlled study design, sensitivity analyses were performed, with similar findings.^5,6

Adverse effects:
The most common serious adverse effects associated with eflornithine in clinical trials were hepatotoxicity, neutropenia, anaemia and hearing loss. Other common adverse effects include otitis media, upper and lower respiratory tract infections, diarrhoea, cough, conjunctivitis, vomiting and skin infections.⁵

Practice points:
Prior to initiating treatment with eflornithine, and periodically during treatment, a full blood count, liver function tests and a hearing assessment should be performed.⁵

Dosage and administration:
Eflornithine is administered by mouth twice daily. The recommended dose depends on the patient's body surface area (refer to the approved Product Information for details).⁵ The minimum dose is 192 mg (1 tablet) twice per day, and the maximum dose is 768 mg (4 tablets) twice per day. Lower doses may be used in patients who experience adverse effects. Treatment is continued for 2 years or until disease recurrence or unacceptable toxicity occurs.⁵

Renal impairment affects the pharmacokinetics of eflornithine; dose reduction is required for patients with severe renal impairment (estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m²).⁵

For people unable to swallow tablets, eflornithine tablets may be chewed or crushed and administered with a small amount of liquid.²

Use in pregnancy and breastfeeding:
Eflornithine is classified as Therapeutic Goods Administration pregnancy category B3.⁵ Patients who could become pregnant, or whose sperm could cause their partner to become pregnant, should use effective contraception during treatment with eflornithine and for 1 week after the last dose.⁵ There are no clinical data regarding the use of eflornithine in lactation.⁵

Place in therapy:
Eflornithine provides an additional treatment option that may improve survival for patients with HRNB who have at least partially responded to induction and consolidation therapies including immunotherapy. It has adverse effects that require ongoing monitoring by healthcare practitioners.

This new drug comment was finalised on 13 April 2026. It was prepared by Rohan Elliott, Senior Clinical Editor, Australian Prescriber, and reviewed by Louis Nguyen, Paediatric Transplant and Cellular Pharmacist, Pharmacy Department, Sydney Children's Hospital.

At the time this new drug comment was prepared, an Australian Public Assessment Report was not available from the Therapeutic Goods Administration.

This article is peer reviewed.

 

References

1. Shakeel A, Baloch A, Kumari V, Kazmi SKZ, Aftab K, Abid S, et al. Iwilfin (eflornithine) approved by the FDA as the first and only oral maintenance therapy for high-risk neuroblastoma in adult and pediatric patients: Narrative review. Medicine (Baltimore) 2024;103:e40662.
2. Australian & New Zealand Children's Haematology-Oncology Group (ANZCHOG). ANZCHOG Solid Tumour Group position on eflornithine (DFMO) for patients with high-risk neuroblastoma (HR-NB) in Australia and New Zealand. Version 2. ANZCHOG; 2024. [cited 2026 Apr 13]
3. Xu S, Foster J, Wahba A. Established and Emerging Therapies for High-Risk Neuroblastoma. Paediatr Drugs 2026;28:159-75.
4. Castelli S, Schulze F, Thole-Kliesch TM, Astrahantseff K, Barone G, Beck-Popovic M, et al. Current treatment strategies for first relapse of high-risk neuroblastoma. Eur J Cancer 2026;236:116254.
5. Therapeutic Goods Administration. Australian Production Information - IFINWIL eflornithine. Department of Health, Disability and Ageing; 2025. [cited 2026 Apr 13]
6. Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol 2024;42:90-102.

 

The new drug comments in Australian Prescriber are prepared by the editors and reviewed by subject matter experts. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. Before new drugs are prescribed, it is important that more detailed information is obtained from the approved product information, a medicines information centre or some other appropriate source.

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