(07) Safety Comparison of Two Different Dosing Regimens for Oral Eflornithine (DFMO) In Pediatric Solid Tumors

Title: Safety Comparison of Two Different Dosing Regimens for Oral Eflornithine (DFMO) In Pediatric Solid Tumors

Abstract : The ongoing NMTRC006B study utilizes two different doses of oral DFMO for pediatric patients with relapsed/refractory solid tumors. Subjects without central nervous system (CNS) disease receive a dose of 1000 mg/m²/dose twice daily (BID), whereas subjects with a history of CNS disease receive a higher dose of 2500 mg/m²/dose BID based on previous cerebral spinal fluid (CSF) pharmacokinetic data. Herein, the safety profiles of these two doses are compared.
The primary objective is to compare the safety profile of two doses of DFMO; 1000 mg/m²/dose BID and 2500 mg/m²/dose BID.
129 subjects have been treated on the 1000 mg/m² BID dose and 71 subjects on the 2500 mg/m² BID dose; diagnoses include high-risk neuroblastoma, medulloblastoma, ATRT, ETMR, and other rare MYCN, ODC, or LIN28/Let7 driven tumors. Data is collected on all new Grade 2 or higher adverse events (AEs) plus existing AEs that worsen relative to baseline, from administration of DFMO, through resolution.
AEs in the 1000 mg/m² BID (lower dose group) versus the 2500 mg/m² BID (higher dose group) were generally similar with some notable differences. Compared with the lower dose group, the higher dose group had higher incidences of anemia (28.8% versus 3.9%), thrombocytopenia (8.5% versus 0.8%), diarrhea (5.6% versus 1.6%) and hearing loss (14.1% versus 3.9%). The majority of these AEs were effectively managed and resolved with a dose reduction of DFMO.
While the overall AE profiles of the two dosing groups were similar, the higher dose was associated with an increased incidence of certain AEs, including anemia, thrombocytopenia, diarrhea, and hearing loss. These findings highlight the importance of closely monitoring patients receiving higher doses to ensure timely intervention if needed. Therefore, the 2500 mg/m² twice-daily dose, with proper management and support, represents a promising treatment option for patients, particularly for those with disease in their CNS.