Table 2. Anti-tumor activity of regorafenib alone and in combination against pediatric xenografts.

Treatment	Schedule (dose dq)	Tumor (n)	Initial Tumor Volume (mm3)	Td (days)	PR	CR	TFS	TGI (at Day)	p	5 x Vi (days)	TGD (days)	p
ET-1
								D13
Control	0.15 mL x 15d	13	166 (75–426)	3.2	0	0	0			8
Regorafenib	30 mg/kg x 30d	14	221 (93–473)		0	0	0	78%	0.0002	33	25	<0.0001
EW7
								D17
Control	0.15 mL x 24d	6	192 (80–250)	4.9						18.5
Regorafenib	30 mg/kg x 21d x 2 cycles	6	203 (80–414)		0	0	0	93%	0.0152	64	46	0.0022
SJ-N-N8
								D16
Control	0.15 mL x 16d	3	180 (156–377)	3.7	0	0	0			10
Regorafenib	30 mg/kg x 21d	4	242 (198–931)		0	0	0	82%	0.0286	31	21	0.0286
SK-N-AS
								D20
Control	0.15 mL x 20d	9	93 (37–143)	6.3	0	0	0			11.5
Regorafenib	10 mg/kg x 21d	11	95 (45–136)		0	0	0	80%	0.008	25	13	0.0124
Regorafenib	30 mg/kg x 21d	10	85 (53–190)		0	0	0	87%	0.003	27	16	<0.0001
RMS-1
								D13
Control	0.15 mL x 13d	13	184 (75–470)	4.7						9
Regorafenib	10 mg/kg x 34d	13	203 (113–332)		0	0	0	67%	0.0058	22	13	0.0036
Regorafenib	30 mg/kg x 44d	14	175 (74–420)		0	0	0	78%	<0.0001	31	22	<0.0001
Control combination	0.125 mL x 13d + 0.25ml x 5d, 0.15 mL x 8d	12	189 (137–397)		0	0	0	2%	ns	9		ns
Refametinib	25 mg/kg x 5d, 15 mg/kg x 8d	13	176 (73–480)		0	0	0	19%	ns	10	1	ns
Regorafenib + Refametinib	10 mg/kg x 38d + 25 mg/kg x 5d,15 mg/kg x 33d	13	162 (92–375)		0	0	0	73%	0.0005	32	23	<0.0001
IGR-N91-Luc
								D29
Control	0.15 mL x 29d	7		1.7
Regorafenib	30 mg/kg x 29d	7						99%	0.0022
IGRG93
								D11
Control	0.15 mL	10	156 (83–307)	2.9						9
Regorafenib	10 mg/kg x 21d	10	140 (60–391)		0	0	0	86%	ns	27	19	0.0356
Regorafenib	30 mg/kg x 21d	11	200 (67–351)		0	0	0	101%	0.0408	32	23	<0.0001
Control + Radiotherapy	0.15 mL x 21d + 1 Gy x 5d	11	160 (62–311)		4	0	0	100%	ns	19	10	ns
Regorafenib + Radiotherapy	10 mg/kg x 21d + 1 Gy x 5d	10	215 (73–329)		6	3	1	111%	<0.0001	34	25	<0.0001
Regorafenib + Radiotherapy	30 mg/kg x 21d + 1 Gy x 5d	11	195 (68–500)		5	6	0	114%	<0.0001	37	28	<0.0001
IGRM57
								D27
Control	0.15 mL x 29d	6	285 (87–385)	3.7						19
Regorafenib	30 mg/kg x 39d	6	217 (167–262)		5	0	0	108%	0.0043	62	43	0.0307
Control + CPT-11	0.15 mL x 39d + 27 mg/kg x 5d	7	231 (97–287)		5	2	0	108%	0.0012	55	36	ns
Regorafenib + CPT-11	30 mg/kg x 39d + 27 mg/kg x 5d	7	222 (125–444)		1	6	0	111%	0.0012	90	71	0.0005
NEM14
								D28
Control	0.15 mL x 29d	6	117 (79–166)	9	0	0	0			20
Regorafenib	30 mg/kg x 29d	7	159 (80–184)		0	0	0	74%	ns	32	12	ns
Control + Radiotherapy	0.15 mL x 29d + 1 Gy x 5d	7	109 (80–171)		0	0	0	74%	ns	30	10	ns
Regorafenib + Radiotherapy	30 mg/kg x 29d + 1 Gy x 5d	7	150 (91–276)		0	0	0	93%	0.0176	42	22	0.0036

CR, complete regression; PR, partial regression; TGD, tumor growth delay; TGI, tumor growth inhibition; 5xVi, Time to reach five time initial tumor volume; TD, tumor doubling time; TFS, tumor free survivor at day 120; ns, non-significant; Statistical analysis was performed using the non-parametric Mann-Whitney test for experiments with 2 treatment groups and the Kruskal-Wallis test for those with more than 2 groups