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journal article Feb 21, 2008

Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program

John M. Maris ORCID Joshua Courtright Peter J. Houghton Christopher L. Morton E. Anders Kolb Richard Lock Mayamin Tajbakhsh C. Patrick Reynolds Stephen T. Keir ORCID Jianrong Wu ORCID Malcolm A. Smith ORCID
Pediatric Blood & Cancer Vol. 51 No. 1 pp. 42-48 · Wiley
View at Publisher Save 10.1002/pbc.21535
Abstract
AbstractBackgroundSunitinib is an orally bioavailable, multi‐targeted tyrosine kinase inhibitor with selectivity for PDGF receptors, VEGF receptors, FLT3, and KIT.ProceduresSunitinib was tested at concentrations ranging from 0.1 nM to 1.0 µM against 23 cell lines from the PPTP in vitro panel. We also compared sunitinib (53.5 mg/kg) or vehicle administered for 28 days by oral gavage in 46 murine xenograft models representing 9 distinct pediatric cancer histologies.ResultsThe leukemia cell line, Kasumi‐1 (gain‐of‐function KITAsn822Lys mutation) was the only line with an in vitro response to sunitinib (IC50 75.7 nM). Sunitinib significantly prolonged EFS in 19 of 35 (54%) of the solid tumor, and in 3 of 8 (38%) of the ALL xenografts analyzed. Using the PPTP time to event measure of efficacy, sunitinib had intermediate (13) and high (1) levels of activity against 14 of 34 evaluable solid tumor xenografts, including 4 of 6 rhabdomyosarcoma, 4 of 5 Ewing tumor, and 2 of 3 rhabdoid tumor xenografts. Following cessation of treatment for the 14 solid tumor xenografts without tumor events by day 28, tumor growth rate increased in most. The only regression noted to sunitinib in the solid tumor panels was a complete response in a rhabdoid tumor xenograft.ConclusionsSunitinib demonstrated significant tumor growth inhibition against most of the PPTP's solid tumor panels, but little activity against the neuroblastoma and ALL panel. Antitumor activity was manifested primarily as tumor growth delay, consistent with an anti‐angiogenic effect for sunitinib against many of the pediatric preclinical models evaluated. Pediatr Blood Cancer 2008;51:42–48. © 2008 Wiley‐Liss, Inc.
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Metrics
74
Citations
37
References
Details
Published
Feb 21, 2008
Vol/Issue
51(1)
Pages
42-48
License
View
Authors
J
John M. Maris
J
Joshua Courtright
P
Peter J. Houghton
C
Christopher L. Morton
E
E. Anders Kolb
R
Richard Lock
M
Mayamin Tajbakhsh
C
C. Patrick Reynolds
S
Stephen T. Keir
J
Jianrong Wu
M
Malcolm A. Smith
Cite This Article
John M. Maris, Joshua Courtright, Peter J. Houghton, et al. (2008). Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program. Pediatric Blood & Cancer, 51(1), 42-48. https://doi.org/10.1002/pbc.21535
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