Clinical factors related to long-term administration of sorafenib in patients with hepatocellular carcinoma

Figures & data

Table 1 Baseline patient characteristics and previous therapy before administration of sorafenib

Variable	Median (range)
Age	71 (52–87)
Gender (M/F)	75/21
HCV/HBV/others	56/15/25
Aspartate transaminase (U/L)	54 (19–165)
Alanine aminotransferase (U/L)	33 (12–150)
Platelets (per μL)	12 (5–32)
α-fetoprotein (ng/mL)	88.7 (3.2–245,500)
des-gamma-carboxy prothrombin (mAU/mL)	559 (5–75,000)
Child-Pugh classification (5/6/7)	62/30/4
BCLC stage B/C	37/59
Extrahepatic spread (±)	27/69
Macroscopic vascular invasion (±)	30/66
ECOG performance status (0/1/2)	50/44/2
Previous therapy	n (%)
Operation	32 (33)
Percutaneous ethanol injection therapy	11 (11)
Percutaneous microwave coagulation therapy	1 (1)
Radiofrequency ablation	42 (44)
TA(C)E	72 (75)
Transcatheter arterial infusion	19 (20)
Radiation	5 (5)
Efficacy in all patients
Level of response	n (%)
CR	0 (0)
PR	13 (14)
SD	31 (32)
PD	30 (31)
Not evaluable	22 (23)
Response rate	14%
Disease-control rate	46%

Abbreviations: BCLC, Barcelona Clinic Liver Cancer; ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HCV, hepatitis C virus; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; TACE, transarterial chemoembolization.

Figure 1 Overall survival for all patients.

Note: Median overall survival was 11.8 (range 7–763) days.

Figure 2 Relationship between continuation of administration and overall survival.

Note: In the group that continued administration for ≥90 days, overall survival was significantly higher than in the group that discontinued administration within 90 days.

Figure 3 Relationship between continuation of administration and overall survival in patients receiving 200 mg or 400 mg.

Note: In the group that continued administration for ≥90 days, overall survival was significantly higher than in the group who discontinued administration within 90 days. Figures 2 and 3). Therefore, we concluded that treatment with sorafenib for ≥90 days achieves better overall survival, even at a reduced dose.

Table 2 Reasons for discontinuation of sorafenib within 90 days

Adverse events without liver dysfunction	36
Progressive disease	11
Hand-foot skin reaction	3
Diarrhea	3
General fatigue	2
Rash	3
Fever	3
Renal failure	2
Pancreatitis	1
Others	8
Liver dysfunction	15
Liver failure	7
Hepatic encephalopathy	3
Ascites	3
Elevation of AST or ALT	1
Jaundice	1

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase.

Table 3 Risk factors contributing to overall survival (n = 96)

	Subgroup	Univariate analysis			Multivariate analysis
		Risk ratio	95% CI	P value	Risk ratio	95% CI	P value
Age	≥71 or <71	0.74	0.39–1.41	0.36
Gender	Female	1.53	0.94–2.51	0.08
Child-Pugh classification	≥6 or 5	0.54	0.28–1.04	0.06
α-fetoprotein (ng/mL)	<50 or ≥50	1.95	0.94–4.0	0.71
Des-gamma-carboxy prothrombin (mAU/mL)	<400 or ≥400	1.69	0.85–3.3	0.13
Etiology	HCV, others	0.74	0.39–1.41	0.37
PS	≥1 or 0	0.66	0.35–1.27	0.22
BCLC	C or B	0.46	0.22–0.97	0.04	0.96	0.38–2.45	0.94
RFA	0 or ≥1	1.25	0.65–2.40	0.51
TACE	<6 or ≥6	1.5	0.74–3.03	0.26
Tumor volume of liver	<50% or ≥50%	4.41	2.24–8.69	<0.0001	1.70	0.77–3.74	0.19
Macroscopic vascular invasion	None or +	3.06	1.61–5.82	0.006	1.76	0.75–4.09	0.19
Discontinuation	<90 or ≥90	0.1	0.04–0.26	<0.0001	0.13	0.05–0.34	<0.0001
Extrahepatic spread	None or +	1.61	0.83–3.13	0.16

Abbreviations: BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; CR, complete response; RFA, radiofrequency ablation; TACE, transarterial chemoembolization.

Table 4 Risk factors contributing to discontinuation of sorafenib administration within 90 days (n = 82)

	Subgroup	Univariate analysis			Multivariate analysis
		Risk ratio	95% CI	P value	Risk ratio	95% CI	P value
Child-Pugh classification	≥6 or 5	2.10	0.83–5.30	0.11
α-fetoprotein (ng/mL)	<50 or ≥50	0.55	0.22–1.35	0.19
DCP (mAU/mL)	<400 or ≥400	0.39	0.16–0.97	0.04	0.59	0.22–1.60	0.30
Radiofrequency ablation	0 or ≥1	0.78	0.32–1.88	0.58
Tumor volume of liver	<50% or ≥50%	0.08	0.01–0.69	0.02	0.99	0.01–0.91	0.04
Macroscopic vascular invasion	None or +	0.33	0.12–0.87	0.03	0.46	0.15–1.39	0.17
TACE	<6 or ≥6	0.26	0.08–0.83	0.02	0.21	0.06–0.72	0.013
Extrahepatic spread	None or +	1.81	0.67–4.92	0.24

Abbreviations: CI, confidence interval; DCP, des-gamma-carboxy prothrombin; TACE, transarterial chemoembolization.