Pediatric-Friendly Formulations: Critical to Maximizing Benefit of Novel Therapeutics Such as Selumetinib for Children With Neurofibromatosis and Other Neoplasms
Mené sur 36 enfants atteints d'un neurofibrome plexiforme symptomatique, inopérable et associé à la neurofibromatose de type 1, cet essai de phase I/II analyse les caractéristiques pharmacocinétiques du sélumétinib (formulation en granules) et évalue sa toxicité
The ability to administer oral medications to children is critically important. As oncology drug development has exploded in the last decade with multiple new oral therapeutics, the ability to provide appropriate dosing options for children of these agents is essential. Many of these agents are highly insoluble, making liquid/solution formulations challenging. All oral dosage forms must be swallowed whole to ensure the intended dose is administered as a full dose. The splitting of tablets is problematic due to the variable distribution of drug within a tablet, limiting the ability to split a tablet ensuring a known, accurate dose. Capsules pose a challenge, as accurate dosing may not be feasible with commercially available capsule sizes. The availability of appropriate tablet/capsule dosing strengths is a challenge as this is typically driven by adult indication and dose, whereas smaller dosing strengths for pediatric patients have limited availability. The US Food and Drug Administration (FDA) requires measurement of the acceptability of the dosage form as defined by a combination of palatability and swallowability.1 Strategies to use existing adult formulations (capsules, tablets, and intravenous [IV] given orally) are often met with challenges of accurate dosing in children. Crushing of tablets may be a reasonable option if issues of solubility, taste, and palpability can be overcome as well as having the appropriate strength of tablets to allow for accurate dosing in small children. Ensuring adequate doing and exposure is critical to pediatric oncology drug development. Studies must include pharmacokinetics (PK), palatability, and efficacy end points to ensure appropriate dosing in children. Many studies have used IV formulations given orally, demonstrating the challenges of taste/palatability and compliance.2,3 Several studies have attempted to develop non–industry-supported formulations for children with institutional supported compounding strategies to achieve a dosing strategy for children.4,5 These studies are limited in their ability to establish comparable PK exposures and FDA-required acceptability standards.
Journal of Clinical Oncology , éditorial, 2026