Table 4.

Current status of antiangiogenic agents in UM

Drugs affecting angiogenesis	Angiogenic Targets	Main Clinical Studies	Clinical Trial Identifiers
Bevacizumab + Temozolomide	VEGF-A	Piperno-Neumann et al. 2013, 2016 [342, 345]
Bevacizumab + IFN-α2b	VEGF-A + bFGF	Guenterberg et al. 2011 [336]
Thalidomide + IFN-α2b	VEGF-A + TNFα + bFGF	Solti et al. 2007 [337]
Thalidomide + PEG-IFN-α2b	VEGF-A + TNFα + bFGF		Phase II, NCT00238329
Temozolamide + Thalidomide	VEGF-A + TNFα		Phase I/II, NCT00005815
Temozolomide + Thalidomide + Lomustine	VEGF-A + TNFα		Phase II, NCT00072345
Temozolomide + Sunitinib	VEGFR-1–3, PDGFR, KIT		Phase II, NCT01005472
Aflibercept	VEGF-A, −B, PIGF	Tarhini et al. 2011 [146, 193]
Lenalidomide	VEGF, VEGFR-2	Zeldis et al. 2009 [339]
Carboplatin + Paclitaxel + Sorafenib	VEGFR-1–3, PDGFR-β, KIT	Bhatia et al. 2012 [340, 348]
Sorafenib	VEGFR-1–3, PDGFR-β, KIT	Mouriaux et al. 2016 [346] Scheulen et al. 2017 [344]
Sunitinib	VEGFR-1–3, PDGFR, KIT	Mahipal et al., 2012 [341]
Sunitinib vs DTIC	VEGFR-1–3, PDGFR, KIT		Phase II, NCT01551459
Sunitinib vs Valproic Acid	VEGFR-1–3, PDGFR, KIT		Phase II, NCT02068586
Sunitinib + Tamoxifen + Cisplatin	VEGFR-1–3, PDGFR, KIT		Phase II, NCT00489944
Imatinib mesylate	PDGFR, KIT	Hofmann et al. 2009 [338]
Axitinib	VEGFR − 1, −2, −3	Fruehauf et al. 2011 [161]
Cabozantinib	VEGFR-2, c-Met, KIT	Daud et al. 2017 [343, 347]
Cabozantinib vs Temozolomide or DTIC	VEGFR-2, c-Met, KIT	Luke et al. 2020 [349]
Vaccine: Tyrosinase/gp100 ± Interleukin-12	bFGF, VEGFR-3		Phase II, NCT00003339
Vaccine:Tyrosinase/GP100/MART-1 + Interleukin-12 + Alum/GM-CSF	bFGF, VEGFR-3		Phase II, NCT00031733
Nab-paclitaxel + Bevacizumab vs Ipilimumab	VEGF-A		Phase II, NCT02158520

Abbreviations: NAE NEDD8-activating enzyme NAE, bFGF basic fibroblast growth factor, TNFα tumor necrosis factor alpha, PIGF placental growth factor, PEG-interferon Pegylated Interferon, DTIC Decarbazine, GM-CSF granulocyte-macrophage colony-stimulating factor