Abstract NMTRC006B is an expanded access study evaluating eflornithine (DFMO), alone or in combination with other therapies, in patients whose tumors demonstrate increased LIN28 expression, MYCN amplification, or upregulation of ODC, and have completed standard treatments. Literature suggests that ODC/polyamines are critical in oncogenesis, presenting a therapeutic target for treatment and recurrence prevention. This case series investigates DFMO in embryonal tumor with multilayered rosettes (ETMR), a rare and aggressive pediatric brain cancer. Preclinical in vitro studies show reduced ETMR cell proliferation following exposure to DFMO, while in vivo models demonstrate decreased tumor volume and extended survival following treatment. Twenty ETMR patients were enrolled on the study, receiving DFMO at 2500 mg/m² orally twice daily for up to two years. Patients remained on therapy for a median of 187 days (range: 47–730). Enrollment included patients at the end of upfront therapy (n = 6), as well as those with relapsed (n = 8) or refractory disease (n = 6). Ten patients had no evidence of disease at enrollment, while ten presented with measurable disease. Nine of the twenty patients remain in remission. Ninety percent of patients experienced at least one adverse event (AE), with 65% reporting AEs related to DFMO. The most common DFMO-related AEs were anemia (40%), hearing impairment (40%), white blood cell decrease (10%), and alanine aminotransferase elevation (10%). No Grade 4 or 5 related toxicities were observed. Two patients required dose reductions due to anemia, which subsequently improved. Among patients with hearing loss, outcomes included resolution without intervention, stable hearing loss not requiring dose adjustment, improvement following dose reduction (n = 2), or stable hearing loss. While the cohort size is small, findings suggest that DFMO shows promise as a chemopreventative agent in ETMR patients, with encouraging remission rates and manageable safety concerns. A larger investigation is needed to validate these preliminary results.
Hanson et al. (Fri,) studied this question.