Table 2.

Neurotoxicities in pediatric clinical trials of biologic agents targeting receptor tyrosine kinases and downstream signal transduction pathways, including all published Children's Oncology Group and Pediatric Brain Tumor Consortium trials

Class	Drug	Trial	Phase	Study Population	Number of Patients	Neurotoxicity
EGFR inhibitors	Erlotinib (Tarceva)	COG-ADVL0214 [5]	I	Solid tumors	46	None
		SJHGO4 [6]	I	HGG	25	None
		ITCC trial [7]	I	BSG, other BT	51	Intratumoral hemorrhage
	Gefitinib (Iressa)	COG-ADVL0016 [12]	I	Solid tumors	25	Intratumoral hemorrhage
		PBTC-007 [13]	I	BSG, HGG	20	Intratumoral hemorrhage
		ZD1839 [14]	I	Solid tumors	29	None
		PBTC-00715	II	BSG, HGG	44	Intratumoral hemorrhage
	Lapatinib (Tykerb)	PBTC-016 [17]	I	Refractory CNS	59	None
PGFR inhibitors	Imatinib (Gleevac)	COG-AALL0031 [20]	I	Ph + ALL	15	None
		COG-AAML0123 [21]	I	Ph + AML	31	None
		PBTC-006 [22]	I	BSG, HGG	27	Intratumoral hemorrhage
VEGF inhibitors	Bevacizumab (Avastin)	PBTC-022 [42]	II	HGG, BSG	31	None
Farnesyltransferase inhibitors	Tipifarnib (Zarnestra)	COG-ADVL0116 [50]	I	Leukemia	29	Rare headache, dizziness
		PBTC-014 [51]	I	BSG	17	Microhemorrhages, Klüver-Bucy syndrome
		COG-ACNS0226 [53]	II	HGG, PNET, BSG	91	Rare motor neuropathy Seizure, headache, altered mental status
Raf inhibitors	Sunitinib (Sutent)	COG-ADVL0612 [30]	I	Solid tumors	23	Fatigue

Abbreviations:

AALL = Adolescents with acute lymphoblastic leukemia

AAML = Adolescents with acute myelogenous leukemia

ADVL = Adolescents with refractory leukemias

BSG = Brainstem glioma

BT = Brain tumor

CML = Chronic myelogenous leukemia

COG = Children's Oncology Group

CNS = Central nervous system

EGFR = Epidermal growth factor receptor

GBM = Glioblastoma

HGG = High-grade glioma

ITCC = Innovative Therapies for Children With Cancer

PBTC = Pediatric Brain Tumor Consortium

Ph+ ALL = Philadelphia chromosome positive acute lymphoblastic leukemia

Ph+ AML = Philadelphia chromosome positive acute myelogenous leukema

VEGF = Vascular endothelial growth factor