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

Area of Science:

• Pediatric Oncology
• Pharmacology
• Cancer Research

Background:

• Sunitinib is an orally bioavailable, multi-targeted tyrosine kinase inhibitor.
• It targets PDGF receptors, VEGF receptors, FLT3, and KIT.

Purpose of the Study:

• To evaluate the in vitro and in vivo efficacy of sunitinib in pediatric cancer models.
• To assess sunitinib's activity against various pediatric cancer histologies.

Main Methods:

• Sunitinib was tested in 23 pediatric cancer cell lines in vitro.
• Sunitinib efficacy was evaluated in 46 murine xenograft models across 9 pediatric cancer types.
• Drug administration was via oral gavage for 28 days.

Main Results:

• Kasumi-1 leukemia cell line with a KIT mutation showed in vitro response (IC50 75.7 nM).
• Sunitinib significantly prolonged event-free survival in 54% of solid tumor xenografts and 38% of ALL xenografts.
• Activity was observed against rhabdomyosarcoma, Ewing tumor, and rhabdoid tumor xenografts, with one complete response in a rhabdoid tumor.

Conclusions:

• Sunitinib demonstrated significant tumor growth inhibition in most pediatric solid tumor models.
• Activity was limited against neuroblastoma and ALL models.
• The primary antitumor effect was tumor growth delay, suggesting an anti-angiogenic mechanism.