Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

Table 2 Positive human epidermal growth factor receptor 2 status by immunohistochemistry and/or fluorescence in situ hybridization for the patients enrolled in the ToGA trial[10,11,27]

AuthorCountries	Year,Type of publication	N° patientsrandomization	SiteStage	Regimen	Response rate	Resectability rate	Survival rate (HR; p)	Node dissection (D1,D2, others)
Yonemura et al[29] Japan	1993 Abstract	55 Tot 29 NAC + S 26 S	GC IV	PMUE	Adv NAC + S	Adv NAC + S	Adv NAC+S Rates NR	NR
Shchepotin et al[30] Ukraine	1995 Abstract	146 Tot 50 S 49 IVCH + S 47 IACH + S	GC NR	NR	Adv IACH + S	Adv IACH + S	Adv IACH + S P < 0.001	NR
Kang et al[31] South Korea	1996 Abstract	107 Tot 54 S 53 NAC + S	GC III/IV	PEF	NR	Adv NAC + S	No difference P = 0.114	NR
Lygidakis et al[32] Greece	1999 Paper	59 Tot 19 S 20 NAC + S + IVCH 20 NAC + S	GC All stages	Mitomycin-C + 5-FU + FA + Farmorubicin	NR	NR	Adv NAC + S + IVCH	NR
Takiguchi et al[33] Japan	2000 Abstract	262 Tot 139 S 123 NAC + S	GC III/IV	5FU + CDDP	Adv NAC + S	Adv NAC+S	Adv NAC + S P = 0.0996	NR
Wang et al[22] China	2000 Paper	60 Tot 30 S 30 NAC + S	EGJ NR	5FU	Adv NAC + S	NR	Adv NAC + S P = 0.17	NR
Kobayashi et al[35] Japan	2000 Paper	171 Tot 80 S 91 NAC + S	AGC	FUDR	NR	NR	Adv S P = 0.010	NR
Hartgrink et al[4] The Netherlands	2004 Paper	59 Tot 30 S 29 NAC + S	Proper AGC (not EGC)	FAMTX	32% CR or PR	EQUAL	Adv S 34% S vs 21% NAC + S P = 0.017	At least 15 nodes
Nio et al[36] Japan	2004 Paper	295 Tot 193 S 102 NAC + S	GC All stages > 50% stage I	UFT	NR	NR	Overall No Adv. NAC + S P = 0.6878 stage II/III -pN + Adv. NAC + S P = 0.0486	D2 48% S 56% NAC + S
Zhao et al[37] China	2006 Paper	60 Tot 20 5’-DFUR 20 5FU + CF 20 S	GC All stages	5’-DFUR Or 5FU+CF	5’-DFUR and 5FU + CF increase AI and reduce PI	NR	NR	NR
Cunningham et al[17] United Kingdom	2006 Paper	503 Tot 250 S 253 NAC + S	GC, EGJ, LE All stages	Epirubicin Cisplatinum 5-FU	Diameter 5 cm vs 3 cm P < 0.001 T1 + T2 stages > NAC + S P = 0.002	NR	Adv NAC + S OS/DFS 23% S 36.3%/NAC+S HR 0.75/0.66 P = 0.009/0.001 more evident for EGJ	D2 40% S 42% NAC + S
Schumacher et al[15] Germany	2010 Paper	282/144 Tot 72 S 72 NAC + S	GC, EGJ (Siewert II, III) stages III, IV	Cisplatinum + FF	Adv in S Tumor length, thickness and width and P Stages more	R0 67% S 81.9% NAC + S P = 0.036 LN + 76.5% S 61.4% NAC + S P = 0.018	No Adv NAC + S 52 ms S 64 ms NAC + S HR = 0.84 P = 0.46	D2 94% 92.6% S 95.7% NAC + S
Imano et al[38] Japan	2010 Paper	63 Tot 16 S 15 CDDP 16 5-FU 16 5-FU + CDDP	GC NR	5FU or CDDP or 5F +CDDP	5-FU + CDDP Increases AI Reduces PI	NR	No differences in 4 arms	D2 in all arms
Biffi et al[39] Italy	2010 Paper	240/70 Tot 35 S 34 NAC + S	EGJ (Siewert II, III), AG	TCF	65% CR + PR	Adv NAC + S (P value NR)	not evaluated premature interruption for low accrual	D2 in almost all cases
Qu et al[40] China	2010 Paper	78 Tot 39 S 39 NAC + S	AGC	Paclitaxel and FOLFOX4	Adv NAC + S P = 0.001	Adv NAC + S P = 0.025	Adv NAC+S P = 0.006 at 2 yr	NR
Ychou et al[18] France	2011 Paper	224 Tot 111 S 113 NAC + S	LE,EGJ,GC All stages	CDDP + 5FU	Adv NAC + S P = 0.054	Adv NAC + S P = 0.04	OS (NAC + S/S) = 38/24 HR = 0.69 P = 0.02 DFS (NAC + S/S) = 34/19 HR= 0.65 P = 0.003 more evident for EGJ	D2 recommended No data on the effect of D2 vs other LN dissection

GC: Gastric cancer; NAC: Neoadjuvant chemotherapy; S: Surgery; EGC: Early gastric cancer; AGC: Advanced gastric cancer; EGJ: Esophagogastric junction; LE: Lower esophagus; OS: Overall survival; DFS: Disease free survival; LN: Lymph node; D2: D2 lymphadenectomy; FA: Folinic acid; CR: Complete response; PR: Partial response; 5-FU: 5-fluorouracil; PMUE: Cisplatin + mitomycin C + etoposide +1-(2-tetrahydrofuryl)- + uracil; IVCH: Intravenous (systemic) chemotherapy; IACH: Super selective intra-arterial chemotherapy; PEF: Low dose cisplatinum + epirubicin + 5-fluorouracil; CDDP: Low dose cisplatinum; 5'-DFUR: 5'-deoxy-5-fluorouridine; FAMTX: 5-fluorouracil + doxorubicin + methotrexate; UFT: Tegafur + 5-fluorouracil; FF: d-L-folinic acid+fluouracile; TCF: Docetaxel + cisplatin + fluorouracil; FOLFOX4: 5-fluorouracil + leucovorin + oxaliplatin; Adv: Advantage; NR: Not reported; Tot: Total; AI: Apoptosis index; PI: Cell proliferation index; HR: Hazard ratio.