S-1 in the treatment of pancreatic cancer

Table 1 Pivotal phase III studies of first-line chemothrapy for advanced pancreatic cancer

Ref.	Treatment	n	ORR	PFS/TTP(mo)	MST(mo)
Burris et al[1]	GEM	63	5.4%	9 wkb	5.65b
	5-FU	63	0%	4 wk	4.41
Moore et al[13]	GEM	284	8%	3.55	5.91
	GEM + erlotinib	285	8.6%	3.75d	6.24e
Conroy et al[14]	GEM	171	9.4%	3.3	6.80
	FOLFIRINOX	171	31.6%d	6.4d	11.1d
Von Hoff et al[15]	GEM	430	7%	3.7	6.70
	GEM + nab-paclitaxel	431	23%d	5.5d	8.50d

^bP < 0.01 vs 5-FU;

^dP < 0.01 vs GEM;

^eP < 0.05 vs GEM. PFS: Progression-free survival; TTP: Time to progression; MST: Median survival time; GEM: Gemcitabine; ORR: Objective response rate; 5-FU: 5-fluorouracil; FOLFIRINOX: Oxaliplatin, irinotecan, fluorouracil and leucovorin.

Table 2 Phase II studies of Gemcitabine and S-1 therapy for advanced pancreatic cancer

Ref.	n	Disease extent	ORR	PFS/TTP(mo)	MST(mo)
Nakamura et al[19]	33	Metastatic	48%	5.4	12.5
Ueno et al[20]	54	Metastatic	44.4%	5.9	10.1
Oh et al[21]	38	Metastatic or LA	32%	5.4	8.4
Lee et al[22]	32	Metastatic or LA	44%	4.92	7.89
Kim et al[23]	22	Metastatic or LA	27.3%	4.6	8.5

PFS: Progression-free survival; TTP: Time to progression; MST: Median survival time; LA: Locally advanced; ORR: Objective response rate.

Table 3 Randomized studies of gemcitabine and S-1 therapy vs gemcitabine for metastatic or locally advanced pancreatic cancer

Study	Treatment	n	ORR	PFS (mo)	MST (mo)
GEST[10]	GS	275	29%b	5.7b	10.1
(PIII)	S-1	280	21%a	3.8c	9.7d
	GEM	277	13%	4.1	8.8
GEMSAP[24]	GS	53	18.9%	5.4a	13.5
(rPII)	GEM	53	9.4%	3.6	8.8
JACCRO PC-01[25] (rPII)	GS	53	28.3%b	6.15b	13.7a
	GEM	59	6.8%	3.78	8.0
Sudo et al[26]	GS	51	21.6%a	5.3a	8.6
	GEM	50	6.0%	3.8	8.6

^aP < 0.05 vs GEM;

^bP < 0.01 vs GEM;

^cP < 0.05 non-inferiority to GEM;

^dP < 0.01 non-inferiority to GEM. PFS: Progression-free survival; MST: Median survival time; GEM: Gemcitabine; GS: Gemcitabine and S-1; ORR: Objective response rate.

Table 4 Phase II studies of S-1 for gemcitabine refractory pancreatic cancer

Ref.	n	ORR	PFS (mo)	MST (mo)
Morizane et al[34]	40	15.0%	2.0	4.5
Sudo et al[35]	21	9.5%	4.1	6.3

PFS: Progression-free survival; MST: Median survival time; ORR: Objective response rate.

Table 5 Randomized phase II studies of S-1 based chemotherapy after gemcitabine failure

Ref.	Treatment group	n	ORR	PFS (mo)	MST (mo)
Mizuno et al[36]	S-1 + irinotecan	60	18.3%	107 d	208 d
	S-1	67	6.0%a	58 d	176 d
Okusaka et al[37]	S-1 + oxaliplatin	134	20.9%	3.0	7.5
	S-1	130	11.5%a	2.8	7.0
Okusaka et al[38]	S-1 + leucovorin	69	27.5%	3.8	6.3
	S-1	71	19.7%	2.7b	6.1

^aP < 0.05 vs S-1;

^bP < 0.01 vs S-1. PFS: Progression-free survival; MST: Median survival time; ORR: Objective response rate.

Table 6 Phase II studies of S-1 and radiotherapy for locally advanced pancreatic cancer

Ref.	n	ORR	PFS/TTP (mo)	MST (mo)
Sudo et al[47]	34	41%	8.7	16.8
Ikeda et al[48]	60	27%	9.7	16.2
Shinchi et al[49]	50	30%	6.7	14.3
Kim et al[50]	25	24%	6.5	12.9

PFS: Progression-free survival; TTP: Time to progression; MST: Median survival time; ORR: Objective response rate.

Table 7 Randomized phase III studies of adjuvant therapy in pancreatic cancer

Study	Treatment	Endpoint	n	DFS(mo)	MST(mo)
ESPAC-1[55]	CRT (5-FU + RT)	OS	145	10.7	15.9
	No CRT		144	15.2a	17.9
	5-FU + leucovorin		147	15.3c	20.1b
	No chemotherapy		142	9.4	15.5
CONKO-001[56]	GEM	DFS	179	13.4d	22.1
	Surgery alone		175	6.9	20.2
JSAP-02[58]	GEM	OS	58	11.4e	22.3
	Surgery alone		60	5.0	18.4
ESPAC-3[59]	GEM	OS	537	14.3	23.6
	5-FU + folinic acid		551	14.1	23.0
JASPAC-01[11,12]	GEM	OS	191	11.2	25.9
	S-1		187	23.2f	NAf

^aP < 0.05 vs CRT;

^cP < 0.05 vs No chemotherapy;

^bP < 0.01 vs No chemotherapy;

^dP < 0.01 vs Surgery alone;

^eP < 0.05 vs Surgery alone;

^fP < 0.01 vs GEM. DFS: Disease-free survival; MST: Median survival time; NA: Not available; OS: Overall survival; 5-FU: 5-fluorouracil.