Table 4.

Pharmacokinetic Parameters of FTD, FTY, and TPI at Level 1 and Level 2 (mean ± SD)

PK Parameters		Level 1 (50 mg/m2/day)		Level 2 (60 mg/m2/day)
		Irinotecan Plus TAS-102 (N = 7)	TAS-102 Alonea (N = 3)	Irinotecan Plus TAS-102 (N = 3)	TAS-102 Alonea (N = 3)
FTD	Cmax (ng/mL)	2740 ± 770	2450 ± 1021	3290 ± 1380	3677 ± 1459
	Tmax (hr)	1.18 ± 0.85	1.5 ± 0.9	1.33 ± 0.76	1.2 ± 0.8
	AUC0-t (hr.ng/mL)	5277 ± 1673	NR	6672 ± 1383	NR
	AUC0-inf (hr.ng/mL)	5322 ± 1684	4297 ± 1387	6823 ± 1508	8435 ± 1645
	t½ (hr)	1.67 ± 0.31	1.49 ± 0.59	2.10 ± 0.36	1.88 ± 0.73
	CL/F (L/hr/kg)	0.143 ± 0.088	0.178 ± 0.055	0.129 ± 0.028	0.103 ± 0.014
	Vd/F (L/kg)	0.361 ± 0.267	0.384 ± 0.175	0.385 ± 0.070	0.273 ± 0.089
FTY	Cmax (ng/mL)	614 ± 94	645 ± 23	856 ± 274	753 ± 293
	Tmax (hr)	1.64 ± 0.69	1.5 ± 0.9	1.83 ± 0.76	1.5 ± 0.9
	AUC0-t (hr.ng/mL)	1859 ± 187	NR	2867 ± 198	NR
	AUC0-inf (hr.ng/mL)	1900 ± 192	1915 ± 327	2958 ± 182	2710 ± 559
	t½ (hr)	1.91 ± 0.41	1.18 ± 0.18	1.77 ± 0.14	1.62 ± 0.32
TPIb	Cmax (ng/mL)	82.7 ± 30.0	54.2 ± 28.5	89.5 ± 11.4	136.1 ± 77.5
	Tmax (hr)	1.86 ± 0.56	1.7 ± 0.6	2.50 ± 0.00	2.7 ± 1.2
	AUC0-t (hr.ng/mL)	256 ± 100	NR	382 ± 20	NR
	AUC0-inf (hr.ng/mL)	265 ± 103	222 ± 79	414 ± 30	542 ± 360
	t½ (hr)	2.05 ± 0.30	1.78 ± 0.27	2.17 ± 1.13	1.66 ± 0.37
	CL/F (L/hr/kg)	1.40 ± 0.83	1.66 ± 0.56	0.978 ± 0.072	0.91 ± 0.40
	Vd/F (L/kg)	4.29 ± 2.88	4.31 ± 1.85	2.99 ± 1.33	2.06 ± 0.62

Abbreviations: FTD trifluridine (α,α,α‑trifluorothymidine), FTY trifluorothymine, NR not reported, SD standard deviation; SN‑38 = 7‑ethyl-10‑hydroxycamptothecin; and TPI = tipiracil hydrochloride (thymidine phosphorylase inhibitor)

^aPhase I study of TAS-102 monotherapy. TAS-102 was administered twice daily, after the morning and the evening meal, for 5 days a week with 2 days rest for 2 weeks, followed by a 14-day rest

^bConcentrations of TPI was obtained as those of hydrochloride