Table 4.

In vivo anti‐tumour efficacy of pyridostatin, NU‐7441, paclitaxel and their combination on HCT116 BRCA2^−/− xenografts.

Treatment	Tumour volume inhibition (%)	Stable disease	Partial response	Complete response	Increase in survival (%) a	Body weight loss (%)	Toxic deaths
NU‐7441	18	0/6	0/6	0/6	8	2	0/6
Pyridostatin	43	0/6	0/6	0/6	29	3	0/6
Paclitaxel	45	0/6	0/6	0/6	38	5	0/6
Pyridostatin + NU‐7441	57	0/6	0/6	0/6	29	4	0/6
Pyridostatin + Paclitaxel	67	3/6	0/6	0/6	58	7	0/6
Pyridostatin + NU‐7441 + Paclitaxel	81	6/6	0/6	0/6	96	8	0/6

Tumours were allowed to grow for 6 days to approximately 220 mm³ before initiation of treatment (day 1). Mice were treated with pyridostatin (i.v.; 7.5 mg/kg/day) at days 1–5 and 8–12 and NU‐7441 (i.p.; 10 mg/kg/day) at days 1–5 and 8–12, 2 h before injection of pyridostatin. Paclitaxel (i.v.; 20 mg/kg) was administered at days 1 and 8 and at days 5 and 12, for the double and triple combinations (Appendix Fig S8). Each experimental group included n = 6 mice. Tumour volume inhibition was calculated at the nadir of the effect using the formula: (1 ‐ [tumour volume in treated mice]/[tumour volume in untreated mice]) x100 and expressed as average for n = 6 mice in each group. Stable disease was defined as mice in which tumour volume did not change for at least 2 weeks after initiation of treatment. Partial or complete responses were defined as mice in which ≥ 50% reduction of tumour volume or tumour disappearance, respectively, were observed for at least 2 weeks after initiation of treatment. Increase in survival was calculated by comparing median survival of treated relative to untreated mice (%). Body weight loss is reported as weight at the end of treatment relative to the first day of treatment (%), as average for n = 5 mice in each group.

^a Animals were euthanised for ethical reasons when tumours reached a mean of 1.7–2 cm³ in volume.