Journal Article

DKFZ-2023-01401

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Key pharmacokinetic parameters of 74 pediatric anticancer drugs providing assistance in preclinical studies.

Jamaladdin, N. (First author)DKFZ* ; Sigaud, R.DKFZ* ; Kocher, D.DKFZ* ; Kolodziejczak, A.DKFZ* ; Nonnenbroich, L.DKFZ* ; Ecker, J.DKFZ* ; Usta, D.DKFZ* ; Benzel, J. ; Peterziel, H.DKFZ* ; Pajtler, K. W. ; van Tilburg, C. M.DKFZ* ; Oehme, I.DKFZ* ; Witt, O. (Last author)DKFZ* ; Milde, T. (Last author)DKFZ*

2023
Wiley-Blackwell Hoboken, NJ

Abstract: Novel drug treatments for pediatric cancer patients are urgently needed. Success of drug development in pediatric oncology has been promising, but many drugs still fail in translation from preclinical to clinical phases. To increase the translational potential, several improvements have been implemented, including the use of clinically achievable concentrations in the drug testing phase. While pharmacokinetic (PK) parameters of numerous investigated drugs are published, a comprehensive PK overview of the most common drugs in pediatric oncology could guide preclinical trial design and improve the translatability into clinical trials. A mini literature review was conducted for PK parameters of 74 anticancer drugs, from the drug sensitivity profiling library of the INdividualized Therapy FOr Relapsed Malignancies in Childhood (INFORM) registry. PK data in the pediatric population were reported and complemented by adult parameters when no pediatric data was available. In addition, blood-brain barrier (BBB)-penetration assessment of drugs was provided by using the BBB-Score. Cmax was available for 73 (97%), AUC for 69 (92%), PPB for 66 (88%), T1/2 for 57 (76%), Tmax for 54 (72%), Cl for 52 (69%), Vd for 37 (49%), Ctrough for 21 (28%) and Css for 4 (5%) of drugs. Pediatric PK data were available for 48 (65%) drugs. We provide a comprehensive review of PK data for 74 drugs studied in pediatric oncology. This data set can serve as a reference to design experiments more closely mimicking drug PK conditions in patients, and may thereby increase the probability of successful clinical translation.

Note: #EA:B310#LA:B310# /2023 Oct;114(4):904-913

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Contributing Institute(s):

1. KKE Pädiatrische Onkologie (B310)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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