Table 1.

Angiogenesis inhibitors

GroupNameActionMTD/phase II dose as single agent
VEGFR and PDGFR TKIsAEE788VEGFR-2, EGFR550 mg qd
Axitinib (AG-013736)VEGFR-1,2,3; PDGFR-β; c-KIT5 mg b.i.d.
Intedanib (BIBF 1120)VEGFR-1,2,3; PDGFR-α,β250 mg b.i.d.
Brivanib (BMS-540215)VEGFR-2,3; FGFR1,2800 mg qd
Cediranib (AZD2171)VEGFR-1,2,345 mg qd
CP 547,632VEGFR-2200 mg qd
Dovitinib (TKI258)VEGFR-1,2,3; PDGFR-β; c-KIT; FLT3; FGFR1,2,3125 mg qd
Motesanib (AMG706)VEGFR-1,2,3; PDGFR-β; c-KIT125 mg qd
OSI 930VEGFR-2; c-KIT500 mg b.i.d.
Pazopanib (GW786034)VEGFR-1,2,3; PDGFR; c-KIT800 mg qd
Semaxinib (SU5416)VEGFR-2, RET145 mg/m2 q1w
Sorafenib (BAY 43-9006)VEGFR-2,3; PDGFR-β, RET, c-KIT, RAF400 mg b.i.d.
SU6668VEGFR-2; FGFR1, c-KIT, PDGFR-β100 mg/m2
Sunitinib (SU11248)VEGFR-1,2; PDGFR-β; c-KIT; FLT3; PDGFR-α,β50 mg qd 4w/6w
Telatinib (BAY 57-9352)VEGFR-2,3; PDGFR-β900 mg b.i.d.
Vandetanib (AZD6474)VEGFR-2, EGFR300 mg qd
Vatalanib (PTK/ZK)VEGFR-1,2,3; PDGFR; c-KIT1200 mg qd
Anti-VEGFRRamucirumab (IMC-1121B)mAb against VEGFR-213 mg/kg q1w
Anti-VEGFAflibercept (VEGF-trap)Soluble VEGFR-1,24 mg/kg q2w i.v.
1600 μg/kg q1w s.c.
BevacizumabmAb against VEGF-A5–15 mg/kg q2w
VEGF-AS (Veglin)VEGF antisense oligonucleotide85 mg/m2 days 1–5 q2w
VDAABT-751Tubulin binding250 mg qd; 150 mg b.i.d.
ASA404 (DMXAA)Flavonoid1000–2000 mg/m2 q1w
CYT 997Tubulin binding202 mg/m2 q3w
EPC2407Tubulin binding13 mg/m2 days 1–3 q3w
Fosbretabulin (CA4P)Tubulin binding52 mg/m2 days q3w
MN-029Tubulin binding180 mg/m2 q1w (3w/4w)
MPC-6827Tubulin binding3.3 mg/m2 q1w
NPI-2358Tubulin binding30 mg/m2 q1w (3w/4w)
Ombrabulin (AVE8062)Tubulin binding22 mg/m2 q3w
OXi4503 (CA1P)Tubulin bindingND
TZT 1027Tubulin binding2.7 mg/m2 q3w
ZD 6126Tubulin binding80 mg/m2 q2w
Integrin inhibitorsATN-161Anti-α5β116 mg/kg 3x/q1w
CilengitideAnti-αvβ3 and anti-αvβ5600 mg/m2 2x/q1w
(EMD 121974)
CNTO95Anti-αv10 mg/kg days 0, 28, 35, and 42, and q3w thereafter
EtaracizumabAnti-αvβ36 mg/kg 2x/q1w
VolociximabAnti-α5β115 mg/kg q1w
MMP inhibitorsBMS-275291MMP-1, -2, -7, -9, -141200 mg qd
Marimastat (BB-2516)Pan-MMP inhibitor50 mg b.i.d.
Metastat (COL-3)MMP-2, -950 mg/m2 qd
MMI270 (CGS27023A)MMP-1, -2, -3, -9, -13300 mg b.i.d.
Neovastat (AE-941)MMP-2, -9, -12240 mL qd
Prinomastat (AG3340)MMP -2, -3, -9, -13, -145–10 mg b.i.d.
Tanomastat (BAY 129566)MMP-2, -3, -9800 mg b.i.d.
Anti-NOTCH-DLL4MK-0752NOTCH inhibitorND
PF-03084014γ Secretase inhibitorND
RO4929097γ Secretase inhibitorND
REGN421Anti-DLL4ND
OMP-21M18Anti-DLL4ND
Anti-EGFL-7MEGF0444AmAb against EGFL-715 mg/kg
Targeting ANG-Tie pathwayAMG 386ANGPT-1, 2 inhibitorND (>30 mg/kg q1w)
CVX-060ANGPT-2 inhibitor15 mg/kg

Abbreviations: b.i.d., twice a day; MMP, matrix metalloproteinase; MTD, maximum tolerated dose; ND, not determined; q1w, once a week; q2w, every 2 weeks; q3w, every 3 weeks; qd, daily.