Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma

Table 1 Inhibitory effect of Gefitinib or/and CDDP on mouse implanted H22 tumors (mean).

Groups	n		Weight of tumor (g)		IR (%)
	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2
Lecithin control	14	14	1.39±0.70	1.42±0.41	0	0
NS control	13	14	1.49±0.80	1.41±0.46	0	0
CDDP d1-5	14	13	0.68±0.27	0.81±0.30	54	43
CDDP d6-10	12	14	0.80±0.25	0.96±0.32	46	32
Gefitinib d1-10	14		0.88±0.28		41
Gefitinib d1-5		14		0.99±0.39		30
Gefitinib d1-10+CDDP d1-5	13		0.66±0.24		56
Gefitinib d1-10+CDDP d6-10	14		1.11±0.41b		26b
Gefitinib d1-5+CDDP d1-5		14		0.63±0.35		56
CDDP d1-5→Gefitinib d6-10		13		0.55±0.25b		61b
Gefitinib d1-5→CDDP d6-10		13		0.90±0.30		36

^bP<0.01 vs Gefitinib d1-10+CDDP d1-5, or Gefitinib d1-5→CDDP d6-10 group, IR: inhibitory rate, CDDP: cisplatin, Exp 1: the first experiment, Exp 2: the second experiment.

Table 2 Effect of Gefitinib or/and CDDP on the amount of peripheral blood cells of mice bearing H22 tumors (mean±SD).

Groups	n		WBC (109/L)		RBC (109/L)		HB (g/L)		PLT(109/L)
	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2
Lecithin control	14	14	7.6±1.8	8.5±1.8	6.8±2.3	7.5±1.1	110.2±14.8	126.6±16.5	1259.1±336.4	1051.4±208.7
NS control	13	14	7.6±1.7	8.4±1.7	6.5±3.2	8.0±1.8	108.4±14.0	125.2±13.5	1149.2±304.4	1057.1±200.4
CDDP d1-5	14	13	6.6±1.8	6.7±2.3a	5.5±3.5a	6.7±0.9a	120.4±16.6	124.5±9.6	542.9±256.4b	589.2±190.3b
CDDP d6-10	12	14	7.7±1.4	6.8±1.9	5.9±2.8	6.7±1.1	117.2±9.8	122.6±18.6	1318.7±829.8	1100.1±281.9
Gefitinib d1-10	14		8.2±2.8		6.2±3.8		116.3±15.6		1203.3±310.5
Gefitinib d1-5		14		9.9±2.5		7.7±1.2		127.9±15.2		1100.3±170.6
Gefitinib d1-10	13		7.2±2.9		6.4±2.3		124.0±16.7		523.8±252.9b
+CDDP d1-5
Gefitinib d1-10	14		7.7±2.5		6.8±1.2		123.9±8.3		1307.5±474.4
+CDDP d6-10
Gefitinib d1-5		14		8.2±2.4		6.9±1.3		122.9±18.6		589.9±168.4b
+CDDP d1-5
CDDPd1-5		13		7.8±1.7		7.3±1.1		126.1±19.3		514.4±204.3b
→Gefitinibd6-10
Gefitinib d1-5		13		6.1±1.3a		7.1±1.2		126.5±20.4		1135.8±245.5
→CDDP d6-10

^aP<0.05,

^bP<0.01 vs Gefitinib (d1-5 or d1-10) group, Exp 1: first experiment, Exp 2: second experiment.

Table 3 Effect of Gefitinib or/and CDDP on BW, TI, and SI of mice bearing H22 tumors (mean±SD).

Groups	n		SI		TI		BW prior to treatment (g)		BW at sacrifice (g)		Net BW at sacrifice (g)
	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2	Exp 1	Exp 2
Lecithin control	14	14	92.1±34.9	76.9±18.0	53.9±13.2	45.2±7.9	16.5±1.0	19.5±1.0	26.6±4.2	28.3±2.0	25.1±4.4	27.5±2.0
NS control	13	14	92.7±35.0	75.7±17.2	52.6±14.2	46.3±8.0	16.5±0.9	19.4±0.8	25.6±4.0	28.3±2.0	25.0±3.8	27.5±2.0
CDDP d1-5	14	13	70.2±17.9b	56.0±16.0b	40.3±5.8a	35.9±4.1a	16.6±0.8	19.8±0.9	22.9±1.5	26.9±2.7	22.3±1.3	25.9±2.7
CDDP d6-10	12	14	59.0±11.9b	52.8±12.9b	39.7±4.9a	35.1±6.3a	16.6±0.8	18.9±0.7	22.0±2.1a	25.3±3.0b	21.2±2.1a	24.4±2.9b
Gefitinib d1-10	14		91.3±21.5		46.3±7.7		16.5±0.9		24.6±2.8		23.8±2.9
Gefitinib d1-5		14		83.6±22.5		41.4±8.0		19.7±0.8		28.0±1.4		27.4±1.5
Gefitinib d1-10	13		59.3±32.5b		39.6±5.1a		16.4±1.0		17.6±2.1b		16.9±2.1b
+CDDP d1-5
Gefitinib d1-10	14		51.7±14.5b		39.7±8.4a		16.5±0.9		19.9±1.6b		18.8±1.6b
+CDDP d6-10
Gefitinib d1-5		14		56.4±8.4b		35.8±4.1a		18.9±0.8		24.6±1.4b		23.7±1.4b
+CDDP d1-5
CDDPd1-5		13		54.5±16.4b		34.6±5.8a		19.7±0.7		24.1±2.3b		24.1±2.3b
→Gefitinib d6-10
Gefitinib d1-5		13		46.3±12.6b		34.1±6.1a		18.9±0.7		24.8±2.4b		24.3±2.3b
→CDDP d6-10

^aP<0.05,

^bP<0.01 vs gefitinib (d1-5 or d1-10) group, BW: body weight, SI: spleen index [10 × weight of spleen (mg)/BW(g)], TI: thymus index [10 × weight of thymus (mg)/BW (g)], Exp 1: first experiment, Exp 2: second experiment.