Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

Table 1 Baseline patient characteristics n (%)

Variables	Number of patients
Gender	Male	30 (81)
	Female	7 (19)
Age (yr)	> 70	19 (51)
	≤ 70	18 (49)
Child-pugh class	A	33 (89)
	B	4 (11)
Etiology	HCV	20 (54)
	HBV	11 (30)
	Others	6 (16)
TNM stage	III	16 (43)
	IVa	8 (22)
	IVb	13 (35)
Previous therapies	Yes	31 (84)
	No	6 (16)
AFP (ng/mL)	> 100	20 (54)
	≤ 100	17 (46)
DCP (mAU/mL)a	> 1000	20 (59)
	≤ 1000	14 (41)
Initial dose of sorafenib (mg/d)	800	21 (57)
	< 800	16 (43)
Nursing intervention	Yes	24 (65)
	No	13 (35)

^aDCP values were not available for 3 cases; TNM: Tumor-Node-Metastasis staging system; AFP: α-fetoprotein; DCP: Des-gamma-carboxy prothrombin; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 2 Sorafenib-related adverse events n (%)

Adverse events	Any Grade	Grade 1	Grade 2	Grade 3
Anorexia	29 (78)	8 (22)	10 (27)	11 (30)
Skin toxicitya	27 (73)	6 (16)	8 (22)	13 (35)
Fatigue	23 (62)	3 ( 8)	11 (30)	9 (24)
Diarrhea	20 (54)	9 (24)	8 (21)	3 (8)
Hypoalbuminemia	19 (51)	4 (11)	14 (38)	1 (3)
Weight loss	17 (46)	7 (19)	9 (24)	1 (3)
Hyperbilirubinemia	16 (43)	10 (27)	5 (14)	1 (3)
Decreased platelet count	14 (38)	3 (8)	9 (24)	2 (5)
Hypertension	13 (35)	2 (5)	6 (16)	5 (14)
Alopecia	13 (35)	5 (14)	8 (22)	0 (0)
Anemia	9 (24)	4 (11)	4 (11)	1 (3)

^aSkin toxicity includes hand–foot skin reaction and any kind of rash.

Table 3 Variables associated with overall survival

Variables	Univariate		Multivariate
	HR(95%CI)	P value	HR(95%CI)	P value
Gender, male (vs female)	0.384 (0.147-1.005)	0.051
Age, ≤ 70 yr (vs > 70 yr)	0.491 (0.225-1.071)	0.074	0.354 (0.135-0.933)	0.036
Previous therapy yes (vs no)	0.035 (0.128-0.961)	0.042
DCP, ≤ 1000 mAU/mL (vs > 1000 mAU/mL)	0.416 (0.178-0.974)	0.043
Initial dose of sorafenib, 800 mg (vs < 800 mg)	0.405 (0.185-0.888)	0.024
Adverse events > grade 2
Anorexia - (vs +)	0.374 (0.158-0.888)	0.026
Skin toxicitya + (vs -)	0.278 (0.122-0.635)	0.002	0.267 (0.102-0.701)	0.007
Fatigue - (vs +)	0.404 (0.176-0.924)	0.032
Hypoalbuminemia - (vs +)	0.379 (0.170-0.842)	0.017	0.221 (0.085-0.575)	0.002

^aSkin toxicity includes hand–foot skin reaction and any kind of rash. HR: Hazard ratio; DCP: Des-gamma-carboxy prothrombin. This table only includes variables with P values < 0.15 in univariate analyses.

Table 4 Variables associated with treatment duration

Variables	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age ≤ 70 yr (vs > 70 yr)	0.543 (0.257-1.147)	0.110
Other etiologies (vs HCV infection)	0.411 (0.191-0.886)	0.023
DCP ≤ 1000 mAU/mL (vs > 1000 mAU/mL)	0.402 (0.190-0.851)	0.017
Nursing intervention yes (vs no)	0.577 (0.278-1.198)	0.140	0.398 (0.181-0.874)	0.022
Efficacy, disease control (vs PD)	0.431 (0.206-0.903)	0.026
Adverse events > grade 2 + (vs -)
Skin toxicitya	0.306 (0.139-0.675)	0.003	0.225 (0.095-0.534)	0.001
Diarrhea	0.352 (0.156-0.796)	0.012
Weight loss	0.555 (0.254-1.213)	0.140
Alopecia	0.236 (0.081-0.686)	0.008

^aSkin toxicity includes hand-oot skin reaction and any kind of rash. HR: Hazard ratio; HCV: Hepatitis C virus; DCP: Des-gamma-carboxy prothrombin.This table only includes variables with P values < 0.15 in univariate analyses.