Newly emerging standard chemotherapies for gastric cancer and clinical potential in elderly patients

Table 1 Grade 3/4 side effects in active regimens for advanced gastric cancer

	FAMTX	ECF	EOX	CF	DCF	S1	CS
Anemia	10	8.0-13.1	8.6	26	18	4.0-12.8	26
Thrombocytopenia	8	4.0-4.7	5.2	13	8	0.0-1.3	5
Neutropenia	58	36.0-41.7	27.6	57	82	5.6-11.0	40
Febrile neutropenia	20	8.0-9.3	7.8	12	29	0.0-1.0	3
Diarrhea	7	2.6-6.0	11.9	8	19	3.0-7.7	4
Stomatitis		1.3	2.2	27	21	0.0	1
Hand-foot syndrome	1	3.0-4.3	3.1			0.0	0
Nausea and vomitting	5	10.2-17.0	11.4	17	14	1.0-5.6	11 and 4
Peripheral neuropathy		0.4	4.4	3	8	2.0	0
Lethargy		16.6	24.9	14	19	2.0-5.1	4
Alopecia1	42	44.2-56.0	28.8
Increased creatinine	3	1.0				0.0	0
Ref.	[8]	[8,9]	[9]	[12]	[12]	[16,17]	[16]

¹Alopecia is grade 2 according to CTCAE ver2. FAMTX: 5-FU/Adriamycin/Methotrexate; ECF: Epirubicin/cisplatin/5-FU; EOX: Epirubicin/Oxaliplatin/Capecitabine; CF: Cisplatin/5-FU; DCF: Docetaxel/cisplatin/5-FU; CS: S-1/Cisplatin.

Table 2 Phase III milestone trials of chemotherapy for far advanced gastric cancer and information of the elderly patients

Publication	Trial	Regimens	OS (number)	Selected regimens	Median	Age range	Proportion of elderly patients (70 years old or over)	Ref.	Country
1991	EORTC	5-FU/Adriamycin/MMC (FAM)	4 (79)	FAMTX	58	23-69	No information	[7]	EORTC
		5-FU/Adriamycin/Methotrexate (FAMTX)	6 (81)		57	28-77
1993	Murad et al	FAMTX	9 (30)	FAMTX	58	26-72	No information	[3]	Brazil
		Best supportive care (BSC)	3 (10)		57	30-71
1995	Pyrhönen et al	5-FU/Epirubicin/Methotrexate (FEMTX)	12.3 (21)	FEMTX	58	42-75	No information	[5]	Finland
		BSC	3.1 (20)		58	42-71
1997	Glimelius et al	5-FU/Leucovorin/Etoposide (FLE)	8 (31)	ELF	64	45-75	No information	[4]	Sweden
		BSC	5 (31)		63	40-74
1997	Webb et al	EPI/CDDP/5-FU (ECF)	8.9 (111)	ECF	59	35-79	No information	[8]	UK
		FAMTX	5.7 (108)		60	29-78
2000	Vanhoefer et al	FAMTX	6.7 (133)	Similar efficacy	58	30-74	No information	[44]	EORTC
		ELF	7.2 (132)		59	25-74
		5-FU/CDDP (FUP)	7.2 (134)		57	24-74
2003	JCOG9205	5-FU	7.1 (105)	5-FU	63	27-75	No information	[14]	Japan
		5-FU/CDDP (CF)	7.3 (105)		63	19-75
		UFT/MMC	6 (70)		60.5	30-75
2006	V325	Docetaxel/CDDP/5-FU (DCF)	9.2 (227)	DCF	55	26-79	24%-25%1	[10]	USA
		CDDP/5-FU (CF)	8.6 (230)		55	25-76
2007	JCOG9912	S1	11.4 (234)	S1	64	39-75	No information	[17]	Japan
		5-FU	10.8 (234)		63	24-75
		CPT11/Docetaxel	12.3 (236)		63	32-75
2008	SPIRITS	S1	11 (150)	S1/CDDP	62	28-74	17%	[18]	Japan
		S1/CDDP (CS)	13 (148)		62	33-74
2008	REAL-2	EPI/CDDP/capecitabine (ECX)	9.9 (241)	EOX	64	25-82	No information	[9]	UK
		ECF	9.9 (249)		65	22-83
		EPI/oxaliplatin/capecitabine (EOX)	11.2 (239)		62	25-80
		EPI/oxaliplatin/5-FU (EOF)	9.3 (235)		61	33-78
2008	Al-Batran et al	5-FU/LV/Oxaliplatin (FLO)	10.7 (112)	FLO	64	33-86	41%-45%2	[23]	AIO
		5-FU/LV/CDDP (FLP)	8.8 (108)		64	27-85

¹This is proportion of patients with 65 years old or over;

²This is proportion of patients over 65 years old.

Table 3 Phase III milestone trials of adjuvant therapy for gastric cancer after surgical resection and information of elderly patients

Publication	Trials	Patient eligibility	Successful regimens as adjuvant therapy	Adjuvant effect	Median	Range	Proportion of elderly patients (70 years old or over)	Ref.	Country
2001	INT-116	Pathological stage IB/II/III/IVM0	Surgery + Chemo (5-FU/LV)-Radiation (45Gy)	9% at 3 years	60	25-87	No information	[31]	USA
			Surgery alone		59	23-80
2006	MAGIC	Clinical stage II or more (M0)	Surgery + perioperative EPI/CDDP/5-FU (ECF)	13.6% at 5 years	62	29-85	20.4%	[32]	UK
			Surgery alone		62	23-81	21.3%
2007	ACTS-GC	Pathological stage II/IIIA/IIIB	Surgery + S1	10% at 3 years	63	27-80	25.9%	[34]	Japan
			Surgery alone		63	33-80	22.6%