Anti-angiogenic agents in metastatic colorectal cancer

Table 3 Other anti-angiogenic agents

Ref.	Regimen (line of treatment)	Sample size	Objective response (%)	PFS (mo)	OS (mo)	Serious AE (grade 3-4)5
Samalin et al[73]; Phase I/II	Sorafenib/irinotecan (NEXIRI) (2nd or later line KRAS mutated)	10 (phase I)	64.9 (DCR)	3.7	8	Asthenia, diarrhea, neutropenia, HFS
		54 (phase II)
Tabernero et al[74]; Phase IIb	Sorafenib/mFOLFOX vs Placebo/mFOLFOX (1st line)	198	NA	9.1 vs 8.7	17.6 vs 18.1	Neutropenia, peripheral neuropathy, HFS
				HR, 0.88	HR, 1.13
				P = 0.46	P = 0.51
Starling et al[116]; Phase I	Sunitinib/FOLFIRI (1st line)	37	57.9	NA	NA	Febrile neutropenia neutropenia, anemia, diarrhea, mucosal inflammation, stomatitis, vomiting, lethargy, pyrexia, thrombotic events
Yoshino et al[117]; Phase I	Sunitinib/mFOLFOX6 (1st line)	12 (6 + 6)3	66.7 in each arm	NA	NA	Neutropenia, leukopenia, thrombocytopenia
Saltz et al[118]; Phase II	Sunitinib (refractory setting)	43 (prior bevacizumab)	2.4	2.2 (TTP; prior bevacizumab)	7.1	Fatigue, diarrhea, nausea, vomiting, and anorexia (most common any grade toxicities)
		41 (no prior bevacizumab)	0	2.5 (TTP; no prior bevacizumab)	10.2
Tsuji et al[75]; Phase II	Sunitinib/FOLFIRI (1st line)	71	36.61/42.32	6.71/ 7.22	NR due to early study closure	Neutropenia, leukopenia, thrombocytopenia diarrhea, nausea decreased appetite and fatigue (most common any grade)
Carrato et al[119]; Phase III	Sunitinib/FOLFIRI vs Sunitinib/placebo (1st line)	768	NA	7.8 vs 8.4 HR 1.095 one-sided stratified log-rank P = 0.807	20.3 vs 19.8 HR, 1.171 P = 0.916	Diarrhea, stomatitis/oral syndromes, fatigue, HFS, neutropenia, thrombocytopenia, anemia, febrile neutropenia
Michael et al[79]; Phase I	Vandetanib/mFOLFOX6 (1st or 2nd line)	9 (100 mg/d dose)	44.44	NA	NA	Diarrhea, nausea and lethargy (most common any grade toxicities)
		8 (300 mg/d dose)	NA	NA	NA
Saunders et al[80]; Phase I	Vandetanib/FOLFIRI	11 (100 mg/d dose)	18.18	NA	NA	Diarrhea, nausea fatigue (most common any grade toxicities; were grade 1-2)
	(1st or 2nd line)	10 (300 mg/d dose)	NA	NA	NA
Yang et al[81]; Phase II	Vandetanib/mFOLFOX6 vs Placebo/mFOLFOX6	32 (100 mg/d dose)4	NA	NA	NA	Diarrhea, nausea, thrombocytopenia, peripheral sensory neuropathy (most common any grade toxicities)
		35 (300 mg/d dose)4
Van Cutsem et al[84]; Phase III	FOLFOX 4/Vatalanib vs FOLFOX4/placebo (2nd line)	855	NA	5.6 vs 4.2	13.1 vs 11.9	Neutropenia, HTN, diarrhea, fatigue, nausea, vomiting, dizziness
				HR, 0.83	HR, 1.0
				P = 0.013	P = 0.957
Hecht et al[85]; Phase III	FOLFOX4/Vatalanib vs FOLFOX4/placebo (1st line)	1168	NA	7.7 vs 7.6	21.4 vs 20.5	Neutropenia, HTN, diarrhea, fatigue, nausea, vomiting
				HR, 0.88	HR, 1.08
				P = 0.118	P = 0.260

¹By independent review;

²Investigator initiated review;

³Six patients received sorafenib 2 wk on, 2 wk off and another 6 patients received sorafenib 4 wk on, 2 wk off;

⁴Progression events (objective/clinical progression/death) in vandetanib 100 mg arm vs placebo: 72% vs 65% (HR, 1.21; 2-sided P = 0.53); vandetanib 300 mg arm vs placebo: 77% vs 65% (HR, 1.41; 2-sided P = 0.25);

⁵In study drug containing arm. DCR: Disease control rate; NA: Not available; NR: Not reached; PFS: Progression-free survival; OS: Overall survival; mFOLFOX6: Three fluoropyrimidine regimens-infusional 5FU/LV; HFS: Hand-foot syndrome.