S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer: A meta-analysis

Table 1 Characteristics of four included studies

Ref.	Year	Country	Study design	Treatment groups	No. of patients	Regimen	Mediancycles	EPOCcriteria	Duration
Koizumi et al[16]	2008	Japan	Randomizedphase III study	Group A	148	S-1: 40-60 mg/m2, b.i.d days 1-21 plus cisplatin 60 mg/m2iv, on day 8, q.2.w	4	7	March 2001-Nov 2006
				Group B	150	S-1: 40-60 mg/m2, b.i.d days 1-28, q.2.w	3
Komatsu et al[17]	2011	Japan	Randomizedphase II study	Group A	48	S-1: 40-60 mg/m2,b.i.d days 1-14 plus irinotecan 75 mg/m2 iv, on days 1 and 15, q.4.w	3	6	Aug 2003-April 2007
				Group B	47	S-1: 40-60 mg/m2, b.i.d days 1-28, q.2.w	2
Narahara et al[18]	2011	Japan	Randomizedphase III study	Group A	155	S-1: 80 mg/m2, b.i.d days 1-21 plus irinotecan 80 mg/m2iv, on days 1 and 15, q.5.w	4	6	June 2004-April 2007
				Group B	160	S-1: 80 mg/m2, b.i.d days 1-28, q.6.w	3
Wang et al[19]	2013	China	Randomizedphase II study	Group A	41	S-1: 40-60 mg/m2, b.i.d days 1-14 plus paclitaxed 60 mg/m2iv, on days 1,8 and 15, q.4.w	6	7	Jan 2008-Dec 2011
				Group B	41	S-1: 40-60 mg/m2, b.i.d days 1-14, q.4.w	5

Group A: S-1-based combination therapy; Group B: S-1 monotherapy. EPOC: Effective practice and organisation of care.

Table 2 Characteristics of patients

	Wasaburo 2008		Yoshito 2011		Hiroyuki 2011		Wang 2013
	S-1-based	S-1	S-1-based	S-1	S-1-based	S-1	S-1-based	S-1
Sex
Men	108	116	34	37	110	127	32	30
Women	40	34	14	10	45	33	9	11
Age, yr
Median	62	62	70	63	63	63	63	61
Rang	33-74	28-74	47-78	24-76	33-75	27-75	35-74	31-73
ECOG performances status
0	106	106	38	35	102	109	31	29
1	38	39	10	12	48	46	6	9
2	4	5	NA	NA	5	5	4	3
Body surface area, m2
< 1.25	6	4	3	1	NA	NA	2	3
1.25-1.50	64	63	19	18	NA	NA	19	17
> 1.50	79	83	26	28	NA	NA	20	21
Disease status
Unresectable	118	119	33	33	129	133	NA	NA
Recurrent	30	31	15	14	26	27	NA	NA
Histology
Diffuse type	103	89	25	25	93	88	28	30
Intestinal type	45	60	22	20	61	71	11	10
Other not specified	0	1	1	2	1	1	2	1
Primary tumor
No	53	58	NA	NA	62	67	15	17
Yes	95	92	NA	NA	93	93	26	24

NA: Not applicable; S-1-based: S-1-based combination therapy.

Table 3 Survival in the three trials included in the meta-analysis

Ref.	No. of patients	Median survival (mo)	1-yr survival (%)	HR (95%CI)	P value
Koizumi et al[16]	148 (Group A)	11.0	46.7	0.77 (0.61-0.98)	< 0.0001
	150 (Group B)	13.0	54.1
Narahara et al[18]	47 (Group A)	10.5	44.9	0.86 (0.66-1.11)	0.233
	48 (Group B)	12.8	52.0
Wang et al[19]	160 (Group A)	11.0	46.3	0.55 (0.34-0.90)	0.020
	155 (Group B)	14.0	61.0
Total	355 (Group A)	10.9	46.3	0.77 (0.66-0.91)	0.000
	353 (Group B)	13.4	56.8

Group A: S-1-based combination therapy; Group B: S-1 monotherapy.

Table 4 Progression-free survival in the two trials included in the meta-analysis

Ref.	No. of patients	Median progression-free survival (mo)	HR (95%CI)	P value
Koizumi et al[16]	148 (Group A)	4	0.57 (0.44- 0.73)	< 0.0001
	150 (Group B)	6
Wang et al[19]	160 (Group A)	4	0.60 (0.37- 0.97)	0.0400
	155 (Group B)	6
Total	308 (Group A)	4	0.58 (0.46-0.72)	0.0000
	305 (Group B)	6

Group A: S-1-based combination therapy; Group B: S-1 monotherapy.

Table 5 Outcome of toxicity meta-analysis comparing S-1-based combination therapy vs S-1 monotherapy as first-line treatment in advanced gastric cancer

Toxicity	S-1-based therapy	S-1 monotherapy	OR (95%CI)	Pvalue	Heterogeneity
Grade 3-4	n/N	n/N			Pvalue	I2
Leucopenia	44/392	12/398	4.06 (2.11-7.81)	< 0.01	0.728	0.00%
Neutropenia	127/392	43/398	3.94 (2.70-5.77)	< 0.01	0.334	11.90%
Anaemia	77/392	30/398	5.96 (3.03-11.73)	< 0.01	0.423	0.00%
Thrombocytopenia	11/392	10/398	0.33 (0.10-1.12)	0.076	0.900	0.00%
Anorexia	91/392	47/398	2.40 (0.79-7.28)	0.122	0.000	83.40%
Nausea	41/392	16/398	2.80 (0.92-8.55)	0.070	0.048	62.00%
Fatigue	26/392	20/398	1.35 (0.74-2.46)	0.336	0.506	0.00%
Vomiting	15/392	9/398	1.71 (0.74-3.96)	0.207	0.707	0.00%
Diarrhea	35/392	16/398	2.41 (1.31-4.44)	< 0.01	0.614	0.00%
Stomatitis	7/392	2/398	2.52 (0.71-8.79)	0.151	0.994	0.00%

S-1-based: S-1-based combination therapy.