Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13- cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial
Tweddle, Deborah A.
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Veal, G. J., Tweddle, D. A., Visser, J., Errington, J., Buck, H., Marange, J., Moss, J., et al. (2021). Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13- cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial. Cancers, 13 (8)https://doi.org/10.3390/cancers13081868
(1) Background: 13-cis-retinoic acid (13-CRA) is a key component of neuroblastoma treatment protocols. This randomized crossover study compares the pharmacokinetics (PK), safety and palatability of a novel oral liquid formulation to the current method of extracting 13-CRA from capsules. (2) Methods: Pharmacokinetics was evaluated in two consecutive treatment cycles. Patients were randomized to receive either liquid or capsule formulation on cycle 1 and then crossed over to the alternative formulation on cycle 2. The daily dose was 200 mg/m2, reduced to 160 mg/m2 in patients with weight ≤ 12 kg. (3) Results: A total of 20 children, median (range) age 4.3 (1–11.6) y were recruited. Pharmacokinetic data were pooled and a population model describing the disposition of 13-CRA and 4-oxo-13-CRA was developed. Bioavailability of the liquid formulation was estimated to be 65% higher (95% CI; 51–79%) than the extracted capsule. CmaxSS and AUC(0-12)SS estimates were also significantly higher; mean (95% CI) differences were 489 (144–835) ng/mL and 3933 (2020–5846) ng/mL·h, respectively (p 0.01). There were no significant differences in reported adverse effects. Parents found dosing considerably easier with liquid formulation. (4) Conclusions: The pharmacokinetics, safety and palatability of a new liquid formulation of 13-CRA compares favorably to 13-CRA extracted from capsules. Clinical Trial Registration: clinicaltrial.gov NCT03291080.
neuroblastoma, 13-CRA, pharmacokinetics, liquid
Wellcome Trust (HICF R7-393)
Department of Health England (HICF R7-393)
External DOI: https://doi.org/10.3390/cancers13081868
This record's URL: https://www.repository.cam.ac.uk/handle/1810/321108