Future perspectives on the treatment of hepatocellular carcinoma with cisplatin

Table 1 Systemic chemotherapy

Author	Country and region	Publication year	Treatment schedule	n	RR (%)	PFS (M)	MST (M)	1yrs (%)
Falkson et al[7]	USA	1987	CDDP 75 mg/sq q3w	35	< 17	-	3.2	-
Okada et al[4]	Japan	1993	CDDP 80 mg/sq q4w	26	15.4	-	-	-
Nagahama et al[8]	Japan	1997	CDDP	43	9.3	-	-	-
Ji et al[9]	Korea	1996	CDDP 60 mg/sq q4w	30	13.3	-	7.6	23.5
			IFN-α 3MU im for 3 mo
Leung et al[10]	China	2002	CDDP 20 mg/sq, d1-4	149	16.8	-	7.1	-
			DXR 40 mg/sq, d1
			5-FU 400 mg/sq, d1-4
			IFN-α 5MU SC d1-4 q3w
Yang et al[11]	Taiwan	2004	CDDP 80 mg/sq d1	63	23.8	2.5	4.9	-
			Mitoxantrone 6mg/sq d1
			5-FU 450 mg/sq d1-5 q4w
Ikeda et al[12,13]	Japan	2008	CDDP 80 mg/sq d1	82	22.0	3.2	11.2	43.5
		(2005)	Mitoxantrone 6 mg/sq d1
			5-FU 450 mg/sq d1-5 q4w
Parikh et al[14]	India	2005	CDDP 70 mg/sq d1	30	20.0	4.1	4.8	27.0
			GEM 1250 mg/sq d1, 8 q3w
Yeo et al[15]	China	2005	CDDP 20 mg/sq, d1-4	94	20.9	-	8.7	39.0
			DXR 40 mg/sq, d1
			5-FU 400 mg/sq, d1-4
			IFN-α 5MU. SC d1-4 q3w
Kim et al[16]	Korea	2006	CDDP 60 mg/sq d1	53	16.9	2.7	5.7	-
			EPI 50 mg/sq d1
			UFT 400-600 mg/d PO 3w
			leucovorin 75 mg/d PO 3w q4w
Park et al[17]	Korea	2006	CDDP 60 mg/sq, d1	29	24.1	3.7	7.7	-
			DXR 60 mg/sq, d1
			Capecitabine 2 g/sq per day 2w q3w

PO: Per os; SC: Subcutaneous injection; im: Intramuscular injection; CDDP: Cisplatin; DXR: Doxorubicin; EPI: Epirubicin; 5-FU: 5-fluorouracil; UFT: Tegaful-uracil; GEM: Gemcitabine; IFN: Interferon; RR: Response rate; PFS: Progression free survival; MST: Median survival time; 1yrs: 1 year survival rate.

Table 2 Hepatic arterial infusion chemotherapy

Author	Country and region	Publication year	Treatment schedule	n	RR (%)	PFS (M)	MST (M)	1yrs (%)	2yrs (%)	3yrs (%)	5yrs (%)
Court et al[18]	USA	2002	CDDP 50 mg/sq (+Radiation) q4w	67	37.0	-	10.7	-	-	-	-
Yoshikawa et al[19]	Japan	2008	CDDP 65 mg/sq q6-8w	80	33.8	-	-	67.5	50.8	-	-
Carr[20]	USA	2000	CDDP 125-200 mg/sq q4-8w	26	42.3	-	19.5	-	-	-	-
Chung et al[21]	Korea	2000	CDDP 2 mg/kg q8w	23	14.0	-	2.5	9	-	-	-
			CDDP 2 mg/kg q8w	19	33.0	-	4.4	27	-	-	-
			IFN-α 3MU. SC. 3/w
Patt et al[22]	USA	1994	CDDP 100 mg/sq, d1	29	41.0	-	15.0	-	-	-	-
			DXR 30-35 mg/sq, d1
			FUDR 60 mg/sq, d1-4
			Leucovorin 15 mg/sq, d1-4
Toyoda et al[23]	Japan	1995	CDDP 5-10 mg/24h, d1-7	21	14.0	-	-	61.1	-	-	-
			5-FU 500 mg/24h, d1-7
Okuda et al[24]	Japan	1999	CDDP 10 mg/1h, d1-5	31	70.9	-	-	-	-	45.7	45.7
			5-FU 250 mg/5h, d1-5 q3-6w
Takayasu et al[25]	Japan	2000	EPI 30 mg/sq, d1, 6	30	42.9	-	-	-	-	-	-
			CDDP 50 mg/sq, d2,7
			ETP 60 mg/sq, d3, 4, 5
Tanaka et al[26]	Japan	2000	CDDP 10 mg/1h, d1-5	77	45.5	-	-	55.8	27.6	18.3	-
			5-FU 250 mg/5h, d1-5 q4w
Ando et al[27]	Japan	2002	CDDP 7 mg/sq 1h, d1-5	48	47.9	-	10.2	-	-	-	-
			5-FU 170 mg/sq 5h, d1-5 x4w
Kaneko et al[28]	Japan	2002	CDDP 75 mg/sq, d1, 15	34	45.0	-	-	24	-	-	-
			5-FU 750 mg/sq, d1, 8, 15, 22
			MTX 30 mg/sq, d1, 8, 15, 22
			leucovorin 30 mg/sq, d1, 8, 15, 22
			IFN-α-2b 3MU. SC, 3/w q4w
Sumie et al[29]	Japan	2003	CDDP 10 mg/1h, d1-5	16	56.3	-	32.4	-	-	-	-
			5-FU 250 mg/5h, d1-5 x4w
Tanioka et al[30]	Japan	2003	CDDP 3 mg/sq 0.5 h, d1-7	38	47.4	-	6.1	-	-	-	-
			5-FU 170 mg/sq continuous d1-7
			x4w q5w
Lin et al[31]	Taiwan	2004	CDDP 10 mg/sq d1-5	53	28.3	-	13.2	-	-	-	-
			MMC 2 mg/sq d1-5
			leucovorin 15 mg/sq d1-5
			5-FU 100 mg/sq continuous d1-5
			x2w q3-4w
Yamasaki et al[32]	Japan	2005	CDDP 10 mg/body d1-5	29	48.3	-	11.8	-	-	-	-
			5-FU 250 mg/body d1-5
			leucovorin 12 mg(or isovorin 12.5 or 6.25 mg) d1-5
Nagai et al[33]	Japan	2007	CDDP 10 mg/h d1-5	37	6.7 vs 31.8	-	7.4 vs 16.3	-	-	-	-
			leucovorin 12 mg/h d1-5	(15 vs 22)
			5-FU 250 mg/sq (4 h vs 22 h)
			x4w
Park et al[34]	Korea	2007	5-FU 500 mg/sq d1-3 q4w	41	22.0	7	12.0	-	-	-	-
			CDDP 60 mg/sq d2

SC: Subcutaneous injection; CDDP: Cisplatin; DXR: Doxorubicin; EPI: Epirubicin; 5-FU: 5-fluorouracil; ETP: Etoposide; MTX: Methotrexate; FUDR: floxuridine; IFN: Interferon; RR: Response rate; PFS: Progression free survival; MST: Median survival time; 1yrs: 1 year survival rate.

Table 3 Transcatheter arterial chemoembolization (inc. transcatheter arterial infusion with lipiodol)

Author	Country	Publicationyear	Treatment schedule	Root	n	RR (%)	MST (M)	1yrs (%)	2yrs (%)	3yrs (%)	5yrs (%)
Ikeda et al[40]	Japan	1992	DXR/Lip 10.5 mg1	Lip-TAI	76	23.7	-	68.0	41.0	24.0	-
			MMC/Lip 7.8 mg1 Lip 3.7 mL1
			CDDP 135.7 mg1
Yodono et al[41]	Japan	1992	CDDP 20 mg/sq, d1-5	TAI	14	46.2	27.6	50.0	43.0	34.0	-
			ETP 30-40 mg/sq, d1-5	+Lip-TACE
			5-FU 250 mg/body, d1-26 + CDDP/Lip + GS
			CDDP 50 mg/sq, d2,8	TAI	31	48.4	21.7	77.0	42.0	-	-
			ETP 50-60 mg/sq, d4-6	+Lip-TACE
			DXR 20 mg/sq, d1,7 + CDDP/Lip + GS
Hatanaka et al[42]	Japan	1995	CDDP 50-100 mg	TACE	60	-	-	80.4	65.2	48.6	-
			DXR 20-40 mg
			FUDR 3-5 g + GS
			CDDP 50-100 mg	Lip-TACE	78	-	-	86.3	55.3	34.8	-
			DXR 20-40 mg Lip 4.8 mL1
			FUDR 3-5 g + GS
			CDDP 50-100 mg	Lip-TAI	159	-	-	65.9	50.3	36.2	-
			DXR 20-40 mg Lip 4.9 mL1
			FUDR 3-5 g
Raoul et al[43]	France	1997	CDDP 70 mg (saline 140 mL)/Lip 10 mL + GS	Lip-TACE	64	57.0	-	42.2	22.1	2.8	-
Carr[20]	USA	2002	CDDP 125-200 mg/sq q4-8w + GS	TACE	31	58.1	30.7	-	-	-	-
Shibata et al[44]	Japan	1989	CDDP 20-150 mg (CDDP/Lip: 20 mg/mL)	Lip-TAI	71	46.5	-	55.0	-	-	-
Kawakami et al[45]	Japan	1993	CDDP 50 mg (CDDP/Lip: 10 mg/mL)	Lip-TAI	12	12.5	7.0	-	-	-	-
			CDDP 50 mg (CDDP/Lip: 10 mg/mL) + GS	Lip-TACE	30	45.5	25	81.3	56.8	-	-
Ono et al[46]	Japan	2000	CDDP 50 mg1 (CDDP/Lip: 10 mg/mL) + GS	Lip-TACE	38	45.0	-	-	49.0	-	19.0
			DXR 43 mg1 (20-50 mg)/Lip + GS	Lip-TACE	46	38.0	-	-	31.0	-	6.0
Kamada et al[47]	Japan	2001	CDDP 41 mg1 (15-70 mg)/Lip + GS	Lip-TACE	108	15.0	24.0	81.0	-	41.0	19.0
			(CDDP/Lip: 10 mg/mL)	or Lip-TAI
			DXR 57mg1 (20-100 mg)/Lip + GS	Lip-TACE or Lip-TAI	26	4.0	17.0	67.0	-	18.0	0.0
Maeda et al[48]	Japan	2003	CDDP 70.5 mg1/Lip	Lip-TAI	143	57.3	-	89.2	65.3	48.8	29.6
			(CDDP/Lip: 20 mg/mL)
			CDDP 78.4 mg1/Lip + GS	Lip-TACE	96	62.5	-	85.2	67.0	48.7	24.2
			(CDDP/Lip: 20 mg/mL)
Ikeda et al[5,6]	Japan	2009	CDDP 50 mg1 (20-150 mg)/Lip	Lip-TAI	94	51.1	30.0	81.6	65.2	39.8	18.3
		-2004	(CDDP/Lip: 20 mg/mL)
			CDDP 70 mg1 (30-150 mg)/Lip + GS	Lip-TACE	74	73.0	37.2	87.8	-	52.2	25.0
			(CDDP/Lip: 20mg/mL)
Uyama et al[49]	Japan	2008	CDDP80 mg1 /Lip (40-100mg) + GS	Lip-TACE	24	45.8	-	-	-	-	-
			(CDDP/Lip: 20 mg/mL)
Yamashita et al[50]	Japan	2009	CDDP 35 mg/sq	Lip-TAI	35	57.1	-	-	-	-	-
			(CDDP/Lip: 10-20 mg/mL)

CDDP: Cisplatin, DXR: Doxorubicin; EPI: Epirubicin; ETP: Etoposide; 5-FU: 5-fluorouracil; FUDR: Floxuridine; MMC: Mitomycin C; GS: Gelatin sponge; Lip: Lipiodol; TAI: Trasctheter arterial infusion; TACE: Trasctheter arterial chemoembolization; RR: Response rate; MST: Median survival time; 1yrs: 1 year survival rate.

¹Mean.

Table 4 Randomized control trial (TACE)

Author	Country and region	Publication year	Treatment schedule	Root	n	RR (%)	1yrs (%)	2yrs (%)	3yrs (%)
Group d'Etude	France	1995	CDDP/Lip (70 mg/10 mL) + GS	Lip-TACE	50	16.3	62.0	37.8	-
et de Traitment
du Carcinome
Hepatocellulaire[51]			Conservative management	-	46	5.0	43.5	26.0	-
Lo et al[39]	Hong Kong	2002	CDDP/saline + Lip (1:1),	Lip-TACE	40	39.0	57.0	31.0	26.0
			(median: 10 mg/20 mL/body
			max: 30 mg/60 mL/body) + GS
			conservative management	-	39	6.0	32.0	11.0	3.0

CDDP: Cisplatin; GS: Gelatin sponge; Lip: Lipiodol; TACE: Trasctheter arterial chemoembolization; RR: Response rate; MST: Median survival time; 1yrs: 1 year survival rate.