Efficacy and safety of thalidomide in patients with hepatocellular carcinoma

Table 1 Clinical characteristics of 42 patients with HCC

Characteristic	n	yr	%
Age
Median		67
Range		32-84
Sex
Male	11		26
Female	31		74
Comorbidity
Absent	10		24
Present	32		76
Cirrhosis
Absent	11		26
Present	31		74
Type of hepatitis
Hepatitis B	15		36
Hepatitis C	11		26
Hepatitis B + hepatitis C	1		2
Hepatitis B + hepatitis D	1		2
No record	14		33
TNM stage
I	2		5
II	6		14
IIIA	21		50
IIIB	2		5
IVA	7		17
IVB	4		10
Child-Pugh classification
Grade A	25		60
Grade B	14		33
Grade C	3		7
Okuda stage
I	11		26
II	27		64
III	4		10
CLIP score
0	2		5
1	10		24
2	7		17
3	15		36
4	4		10
5	4		10
6	0		0
α-fetoprotein
> 400 ng/mL	21		50
≤ 400 ng/mL	21		50
Pre thalidomide therapy
TAE1	26		62
PEI + TAE1	3		7
Radiation + TAE1	2		5
Surgery + PEI2	1		2
Chemotherapy	1		2
No therapy	9		21

¹Transarterial embolization;

²Percutaneous ethanol injection.

Table 2 Response rates of HCC to thalidomide

Author	n	Tumor response, n (%)
		CR1	PR2	SD3	PD4	CR1 + PR2 + SD3
Kong et al[14]	11	0	1 (9)	4 (36)	6 (55)	5 (46)
Lin et al[15]	27	0	1 (4)	1 (4)	25 (93)	2 (7)
Feun et al[16]	7	0	0	0	7 (100)	0
Schwartz et al[17]	30	1 (3)	1 (3)	9 (30)	19 (63)	11 (37)
Hsu et al[18]	63	1 (2)	3 (5)	20 (32)	39 (62)	24 (38)
Wang et al[19]	99	0	6 (6)	-	-	-
Chiou et al	42	0	2 (5)	9 (21)	31 (74)	11 (26)

¹Complete response;

²Partial response;

³Stable disease;

⁴Progressive disease.

Table 3 Comparison of patients with partial response or stable disease with patients with progressive disease

Characteristic	PR1 + SD2	PD3	P
	n	n
Sex			1.0
Male	8	23
Female	3	8
Age			0.234
> 60 yr	10	21
≤ 60 yr	1	10
Cirrhosis			0.041a
Absent	0	11
Present	11	20
Hepatitis
Hepatitis B	4	13	1.0
Hepatitis C	3	9	1.0
TNM stage
I + II	3	4	1.0
IIIA + IIIB	4	19	0.180
IVA + IVB	4	8	1.0
Child-Pugh classification
Grade A	5	21	0.280
Grade B	6	8	0.136
Grade C	0	2	1.0
Okuda stage
I	3	8	1.0
II	8	19	0.717
III	0	4	0.558
CLIP score
0-2	7	13	0.298
3-6	4	18	0.298
α-fetoprotein			0.081
> 400 ng/mL	3	19
< 400 ng/mL	8	12
Tumor size			0.034a
≤ 5 cm	7	8
> 5 cm	4	23

¹Partial response;

²Stable disease;

³Progressive disease;

^aP < 0.05 between the two groups.

Table 4 Comparison of thalidomide treatment and survival between the two groups

	PR1+ SD2	PD3	P
Duration (d)	167.1 ± 98.9	107.7 ± 71.7	0.069
Total dose (mg)	22022.7 ± 11461.4	13669.4 ± 8446.0	0.023a
Survival (d)	304.4 ± 167.1	181.0 ± 107.1	0.047c

¹Partial response;

²Stable disease;

³Progressive disease;

^aP < 0.05,

^cP < 0.05 vs duration, between the two groups.

Table 5 Thalidomide-related adverse events in patients with HCC

	Grade of severity (n)					Total
Adverse event	G1	G2	G3	G4	G5	n (%)
Constipation	2	22	0	0	0	24 (57)
Skin rash	6	8	3	0	0	17 (41)
Low leg edema	1	10	0	0	0	11 (26)
Dizziness	3	5	1	0	0	9 (21)
Lethargy	3	2	2	0	0	7 (17)
Nausea/vomiting	1	5	0	0	0	6 (14)
Neurosensory	3	0	0	0	0	3 (7)
Dyspnea	0	2	0	0	0	2 (5)
Leukopenia	1	0	0	0	0	1 (2)
Thrombocytopenic purpura	0	1	0	0	0	1 (2)
Insomnia	0	1	0	0	0	1 (2)
Alopecia	1	0	0	0	0	1 (2)

¹mild adverse event;

²Moderate adverse event;

³Severe adverse event;

⁴Life-threatening or disabling adverse event;

⁵Death related to adverse event.

Table 6 Thalidomide-related adverse events and comorbidity

Adverse drug events per patient	Comorbidity (n)
	Absent	Present
1	3	10
2	1	7
3	2	6
4	0	7

Table 7 Correlation between thalidomide-related adverse events and comorbidity

	Comorbidity (n)		P
	Absent	Present
Without adverse events	4	2	0.021
With adverse drug eventsa	6	30
Adverse events per patientc	1.1 ± 1.2	2.2 ± 1.3	0.022

^aP < 0.05,

^cP < 0.05 vs without adverse events, between groups of with comorbidity and without comorbidity.