Table 2.

Clinical trials of combination of antiangiogenics

Drug 1Drug 2PhaseCancerMTD/phase II doseGrade 3/4 toxicitiesReference
BevacizumabABT-510ISolid tumorsB: BV 10 mg/kg q14dGastrointestinal bleed (4%), headache (4%)(73)
ABT-510: 100 mg b.i.d.
BevacizumabAxitinib (+FOLFOX)ISolid tumorsB: 2 mg/kg q14dHypertension (18%), neutropenia (12%)(71)
A: 5 mg b.i.d.
BevacizumabCombretastatinISolid tumorsB: 10 mg/kg q14dAtrial fibrillation (7%), hemorrhage (7%)(54)
C: 63 mg/m2 q14d
BevacizumabCediranibISolid tumorsB: 5 mg/kg q14dCNS bleed (8%), nausea (6%) and hypertension (6%)(76)
C: 20 mg/day
BevacizumabSorafenibISolid tumorsB: 5 mg/kg q14dHypertension: (33%), diarrhea (12%), fatigue (7%), transaminitis (10%)(63)
S: 200 mg b.i.d.
BevacizumabSorafenibISolid tumorsB: 5 mg/kg q14dHypertension: (18%), diarrhea (12%), transaminitis (12%)(64)
S: 200 mg b.i.d. days 1–5/q1w
BevacizumabSorafenib (+paclitaxel)ISolid tumorsB: 5 mg/kg q14dHypertension (30%), hfs (22%), neutropenia (17%), neuropathic pain, (8%), mucositis (8%)(70)
S: 200 mg b.i.d. days 1–5/q1w
(+P: 80 mg/m2 q1w)
BevacizumabSorafenib (+paclitaxel)ISolid tumorsB: 0–5 mg/kg q14d (dose escalation ongoing)HFS 25%, rash 8%, stomatitis 8%, diarrhea 16%, granulocytopenia 8% hoarseness 8%(69)
S: 200 mg b.i.d.
(+P: 90 mg/m2 d1,8,15 q4w)
BevacizumabSunitinibISolid tumorsB: 5 mg/kg q14dHypertension (47%), fatigue (24%), thrombocytopenia (18%), proteinuria (13%), HFS (13%)(59)
S: 50 mg/qd
BevacizumabSunitinibIRCCB: 10 mg/kg q14dHypertension (65%), proteinuria (39%), thrombocytopenia (29%), HFS (22%), fatigue (13%); 2 cases of severe MAHA(60)
S: 50 mg/qd
BevacizumabVandetanibISolid tumorsB: 5 mg/kg q21dDiarrhea, elevated creatinine, anemia thrombocytopenia, hemorrhage, prolonged QTc interval, proteinuria, rash(57)
V: 200 mg qd
BevacizumabSorafenibIIGBMB: 5 mg/kg q14dfatigue, thrombosis, hypophosphatemia, muscle weakness(65)
S: 200 mg b.i.d. days 1–5/q1w
BevacizumabSorafenibIIMelanomaB: 5 mg/kg q14dHypertension (14.2%), HFS (7%), proteinuria (7%), thrombocytopenia (7%)(67)
S: 200 mg b.i.d. days 1–5/q1w
BevacizumabSorafenibIIColorectalB: 5 mg/kg q14dFatigue (18%), hypertension (14%), rash (8%), elevated lipase (7%)(68)
S: 200 mg b.i.d. days 1–5/q1w
BevacizumabSorafenibIINETB: 5 mg/kg q14dHFS (20%) asthenia (16%)(66)
S: 200 mg/qd
SorafenibAMG-386IIRenalArm A: S: 400 m b.i.d. + A: 10 mg/kgArm A: diarrhea (8%), HFS (12%), and hypertension (18%).(75)
Arm B: S: S: 400 m b.i.d. + A: 3 mg/kgArm B: diarrhea (10%), HFS (16%), hypertension (20%)
Arm C: S: 400 m b.i.d. + placeboArm C: diarrhea (8%), HFS (28%), and hypertension (14%)

Abbreviations: b.i.d., twice a day; CNS, central nervous system; MAHA, microangiopathic hemolytic anemia; MTD, maximum tolerated dose; NET, neuroendocrine tumor; P, paclitaxel; q1w, once a week; q14d, every 14 days; q21d, every 21 days; qd, once a day; S, sorafenib.