Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies

Figures & data

Figure 1 Metabolism of S-1.

Abbreviations: 5-FU, 5-fluorouracil; CDHP, gimeracil; CYP2A6, cytochrome P450 2A6; DPD, dihydropyrimidine dehydrogenase; FUH2, 5-fluorodihydrouracil; FUMP, fluorouridine monophosphate; OPRT, orotate phosphoribosyltransferase; Oxo, oteracil potassium.

Figure 2 Metabolism of capecitabine.

Abbreviations: CE, carboxylesterase; 5′-DFCR, 5′-deoxyfluorocytidine, 5′-DFUR, doxifluridine; 5-FU, 5-fluorouracil; CD, cytidine deaminase; TP, thymidine phosphorylase.

Table 1 The optimal dose of S-1-based chemotherapy

Regimens	Drugs	Dose	Cycle
S-1 alone	S-1	40 mg/m^2, twice a day, on days 1–28	6 weeks
S-1 + CDDP (Japanese dose)	S-1	40 mg/m^2, twice a day, on days 1–28	5 weeks
	CDDP	60 mg/m^2 on day 8
S-1 + CDDP (Western dose)	S-1	25 mg/m^2, twice a day, on days 1–28	4 weeks
	CDDP	75 mg/m^2 on day 1

Abbreviation: CDDP, cisplatin.

Table 2 Adverse events of First-line Advanced Gastric Cancer Study trial

Toxicity	S-1 + CDDP (n = 521)		5-FU + CDDP (n = 508)
	All (%)	Grades 3–4 (%)	All (%)	Grades 3–4 (%)
Anemia	81.6	20.7	78.1	20.9
Neutropenia	60.5*	32.3	82.5*	63.6
Thrombocytopenia	36.8*	8.3	50.5*	13.5
Leucopenia	54.9*	13.7	76.1	33.2
Febrile neutropenia	5.0*		14.4*
Vomiting	48.0**	7.9	55.3**	9.6
Diarrhea	29.2*	4.8	38.4*	4.5
Hypokalemia	6.9*	3.6*	16.7*	10.8*
Stomatitis	6.3*	1.3*	30.3*	13.6*
Mucosal inflammation	3.8*	0.8*	29.9*	8.1*
Calculated CrCL <50 mL/minute	22.6**		40.9**
All toxic deaths	2.5**		4.9**

* Notes: P < 0.01;

** P < 0.05.

Abbreviations: 5-FU, 5-fluorouracil; CDDP, cisplatin; CrCL, creatinine clearance.

Table 3 Results of Phase II trials of S-1-based chemotherapy

Study (region)	Regiment	Number of patients	RR (%)	PFS (months)	MST (months)	P value
JCOG9912 (Japan)	5-FU	234	9	2.9	10.8
	CDDP +	236	38	4.8	12.3	NS
	irinotecan + S-1	234	28	4.2	11.4	Noninferiority
SPIRITS (Japan)	S-1	150	3	4.0	11.3	P < 0.05
	S-1 + CDDP	148	54	6.0	13.0
GC0301/TOP-002 (Japan)	S-1	160	26.9	3.6	10.5	NS
	S-1 + irinotecan	155	41.5	4.5	12.8
START (Japan and Korea)	S-1	313	18.4	4.0	11.7	NS
	S-1 + docetaxel	310	30.3	4.7	13.0
FLAGS (Western)	S-1 + CDDP	521	29.1	4.8	8.6	NS
	5-FU + CDDP	508	31.9	5.5	7.9

Abbreviations: 5-FU, 5-fluorouracil; CDDP, cisplatin; FLAGS, First-line Advanced Gastric Cancer Study; JCOG, Japan Clinical Oncology Group; MST, median survival time; NS, not significant; PFS, progression-free survival; RR, response rate; SPIRITS, Randomized Phase III Study of TS-1 Alone Versus TS-1 Plus CDDP in Advanced Gastric Cancer; START, Randomized Phase III Study of S-1 Alone Versus S-1 Plus Docetaxel in the Treatment for Advanced Gastric Cancer.