S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

Table 1 Baseline characteristics

Study	Year	Country	Number of patients		Treatments
			S-1	non-S-1	Experimental arm	Control arm
Ajani et al[24]	2013	Non-Asian	521	508	S-1: 25 mg/m2, B.i.d, day 1-21; cisplatin: 75 mg/m2, civ 1-3 h, day 1, q.4.w.	5-FU: 1000 mg/m2/24 h, day 1-5; cisplatin: 100 mg/m2, civ 1-3 h, q.4.w.
Huang et al[25]	2013	China	119	110	S-1: 80-120 mg/d, day 1-14; paclitaxel: 60 mg/m2, iv, day 1, 8 and 15, q.4.w.	5-FU: 500 mg/m2, civ, day 1-5; leucovorin 20 mg/m2, iv, day 1-5; paclitaxel: 60 mg/m2, iv, day 1, 8 and 15, q.4.w.
Kim et al[26]	2012	Korea	65	64	S-1: 80 mg/d, day 1-14; Oxaliplatin: 130 mg/m2, iv (2 h), day 1, q.3.w.	Capecitabine: 2000 mg/d, day 1-14; Oxaliplatin: 130 mg/m2, iv (2 h), day 1, q.3.w.
Nishikawa et al[27]	2012	Japan	80	77	(sequential), S-1: 80 mg/m2, day 1-28, 2-wk rest followed by PTX; or (concurrent), S-1: 14 d and PTX: 50 mg/m2, day 1, 8, q.3.w.	(sequential), intravenous 5-FU: 800 mg/m2, iv, day 1-5, followed by weekly PTX at 80 mg/m2; or (concurrent), 5-FU: 600 mg/m2, iv, day 1-5 and weekly PTX at 80 mg/m2, q.4.w.
Jeung et al[20]	2010	Korea	37	38	S-1: 35 mg/m2, B.i.d, day 1-14; doc: 35 mg/m2, day 1, 8, q.3.w.	cisplatin: 35 mg/m2, day 1, 8; doc: 35 mg/m2, day 1, 8, q.3.w.
Boku et al[22]	2009	Japan	234	232	S-1: 40 mg/m2, B.i.d, day 1-28, q.6.w.	5-FU: 800 mg/m2, civ, day 1-5, q.4.w.
Lee et al[23]	2008	Korea	45	46	S-1: 40 mg/m2 (BSA < 1.25 m2), 50 mg/m2 (BSA: 1.25-1.5 m2), 60 mg/m2 (BSA > 1.5 m2), B.i.d, day 1-28, q.6.w.	Capecitabine: 1250 mg/m2, B.i.d, day 1-14, q.3.w.

5-FU: 5-fluorouracil; PTX: Paclitaxel; BSA: Body surface area.

Table 2 Comparison of toxicity between S-1-based chemotherapy and non-S-1-based chemotherapy

Toxicity	Number of Trials	Incidence of toxicity (%)		RR (95%CI)	P value
		S-1 Arm	Non-S-1 Arm
Hematologic
Anemia	6	14.01	14.86	1.150 (0.720-1.837)	0.560
Neutropenia	6	17.54	24.80	1.043 (0.451-2.413)	0.922
Thrombocytopenia	4	3.91	5.22	0.736 (0.499-1.085)	0.121
Leukopenia	6	8.87	9.15	1.334 (0.524-3.397)	0.546
Febrile neutropenia	3	0.86	3.54	0.225 (0.126-0.515)	0.000
Neutropenic infection	3	0.67	0.39	1.450 (0.476-4.424)	0.513
Nonhematologic
Fatigue	6	8.67	8.37	1.041 (0.788-1.375)	0.777
Vomiting	5	4.29	5.61	0.769 (0.530-1.114)	0.164
Nausea	6	5.91	7.38	0.805 (0.583-1.111)	0.187
Diarrhea	6	5.24	3.54	1.288 (0.590-2.813)	0.525
Abdominal pain	2	4.00	2.76	1.469 (0.925-2.335)	0.103
Anorexia	6	7.44	6.99	1.074 (0.790-1.461)	0.647
Weight decreased	2	2.00	3.25	0.625 (0.369-1.061)	0.082
Stomatitis/mucosal inflammation	4	1.53	11.81	0.230 (0.060-0.878)	0.032
Liver function	3	0.86	0.69	1.221 (0.481-3.103)	0.674
Neuropathy, peripheral	5	0.67	0.89	0.724 (0.274-1.915)	0.515
Alopecia	2	0.38	0.30	1.205 (0.300-4.840)	0.792
Palmar-plantar erythrodysesthesia	4	0.38	0.59	0.719 (0.241-2.150)	0.555

RR: Relative risk.

Table 3 Comparison of objective response rate, overall survival, progression-free survival and time-to-treatment failure between S-1-based chemotherapy and 5-FU-based or capecitabine-based chemotherapy

Subgroups	ORR		OS		PFS		TTF
	RR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
S-1 vs 5-FU	1.454 (1.038-2.036)	0.029	0.895 (0.805-0.995)	0.041	0.809 (0.635-1.030)	0.086	0.832 (0.751-0.992)	0
S-1 vs capecitabine	0.952 (0.649-1.397)	0.801	1.090 (0.803-1.481)	0.579	1.036 (0.764-1.405)	0.819	Not applicable	Not applicable

ORR: Objective response rate; OS: Overall survival; PFS: Progression-free survival; TTF: Time-to-treatment failure; 5-FU: 5-fluorouracil.

Table 4 Comparison of toxicity between S-1-based chemotherapy and 5-fluorouracil- or capecitabine-based chemotherapy

Toxicity	S-1 vs 5-FU		S-1 vs capecitabine
	RR	P value	RR	P value
Hematologic
Anemia	1.073	0.794	1.914	0.145
Neutropenia	1.023	0.964	0.475	0.066
Thrombocytopenia	0.683	0.096	0.953	0.903
Leukopenia	0.584	0.002	1.788	0.402
Nonhematologic
Fatigue	1.091	0.558	0.428	0.139
Vomiting	0.801	0.268	0.925	0.928
Nausea	0.791	0.179	1.177	0.812
Diarrhea	1.988	0.436	0.693	0.601
Anorexia	1.057	0.736	1.164	0.794
Weight decreased	0.625	0.082	Not applicable	Not applicable
Stomatitis/mucosal inflammation	0.230	0.032	Not applicable	Not applicable
Neuropathy, peripheral	0.808	0.722	Not applicable	Not applicable
Palmar-plantar erythrodysesthesia	1.770	0.468	0.193	0.133

5-FU: 5-fluorouracil.