Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: Recent advances and future perspectives

Table 1 Current status of clinical trials with agents that target growth factor receptors and related signaling pathways for treatment of gastrointestinal neuroendocrine tumors

Name	Target	Mechanism	Tumor type	Cotreatment	Status	Reference
Bevacizumab	VEGF	VEGF-neutralizing antibody	Carcinoid	Peg IFN-α	Phase II	[35]
			Carcinoid	Depot-octreotide	Phase III	South West Oncology Group: S50518
			Carcinoid	Panzem	Phase II	NCT00227617
			Advanced GEP NET	FOLFOX	Phase I/II	NCT00328497
			Advanced GEP NET	Oxaliplatin, capecitabine	Phase II	NCT00398320
			Pancreatic and other unresectable carcinoid	Temzolomide	Phase II	NCT00137774
Sunitinib	VEGFR, PDGFR, c-KIT, FLT3	Tyrosine kinase inhibitor	Carcinoid		Phase II	[48]
			Carcinoid		Phase II	NCT00428597
			Carcinoid1		Phase II	NCT00434109
Pazopanib	Pan-VEGFR, PDGFR, c-KIT	Tyrosine kinase inhibitor	Low-, intermediate grade GEP NET		Phase II	NCT00454363
AMG706	pan-VEGFR, PDGFR, c-KIT	Tyrosine kinase inhibitor	Low-grade GEP NET		Phase II	NCT00427349
Vatalanib	VEGFR, PDGFR, c-KIT	Tyrosine kinase inhibitor	Progressive GEP NET2		Phase II	[64]
			Progressive GEP NET		Phase II3	NCT00227773
Gefitinib	EGFR	Tyrosine kinase inhibitor	Progressive GEP NET		Phase II	[79]
			Advanced GEP NET	Cetuximab	Phase II	NCT00397384
NVP-AEW541	IGF-1R	Tyrosine kinase inhibitor	NET cells		Pre-clinical	[14]
Everolimus	mTOR	Protein kinase inhibitor	Islet carcinoid		Phase II	[136]
			Carcinoid	Octreotide	Phase II	[127]
Temsirolimus	mTOR	Protein kinase inhibitor	Recurrent, metastatic		Phase II	[137]
			GEP NET
Sorafenib	c-Raf, B-Raf, VEGFR, PDGFR	Tyrosine kinase inhibitor	Progressive, metastatic GEP NET		Phase II	NCT00131911
Imatinib	PDGFR, c-KIT, ABL	Tyrosine kinase inhibitor	Carcinoid		Phase II	[127]
			Advanced GEP NET		Phase II	[59]
Bortezomib	Proteasome	Proteasome inhibitor	Metastatic GEP NET		Phase II	[153]

¹Liver predominant metastases after hepatic arterial embolization;

²Progressive after somatostatin treatment;

³Withdrawn.