Multikinase inhibitor-associated hand-foot skin reaction as a predictor of outcomes in patients with hepatocellular carcinoma treated with sorafenib

Table 1 Baseline characteristics of patients

Patient features	n (%)
Total No. of patients	40
Age (yr)
Median (range)	71 (48-89)
Sex
Male	31 (78)
Female	9 (12)
Child-Pugh class
A	36 (90)
B	4 (10)
Underlying cause
HCV	23 (58)
HBV	10 (25)
Others	7 (17)
Portal vein thrombosis	11 (28)
Liver only	26 (60)
Metastatic disease	24 (40)
AFP (ng/mL)
> 100	26 (65)
≤ 100	14 (35)
DCP (mAU/mL)
> 1000	19 (48)
≤ 1000	21 (52)
BCLC stage
B	16 (40)
C	24 (60)
Intervention by pharmacists
Yes	22 (55)
No	18 (45)

AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; DCP: Des-gamma-carboxy prothrombin; HCV: Hepatitis C virus; HBV: Hepatitis B virus.

Table 2 Adverse events according to Common Toxicity Criteria for Adverse Events v4.0 n (%)

Adverse events	Grade 1	Grade 2	Grade 3	All
MKI-associated HFSR	11 (27)	6 (15)	5 (13)	22 (55)
Anemia	10 (25)	4 (10)	0 (0)	14 (35)
Hypertension	7 (17)	5 (13)	0 (0)	12 (30)
Anorexia	7 (17)	4 (10)	1 (3)	12 (30)
Decreased platelet count	4 (10)	4 (10)	4 (10)	12 (30)
Alopecia	9 (22)	1 (3)	0 (0)	10 (25)
Diarrhea	5 (13)	0 (0)	2 (4)	7 (17)

MKI-associated HFSR: Multikinase inhibitor-associated hand-foot skin reaction.

Table 3 Univariate and multivariate analyses of predictive factors for overall survival

	Univariate analysis		Multivariate analysis
	HR	P value	HR	P value	95%CI
Age (≥ 65 yr)	0.494	0.079
Initial dose (800 mg)	1.635	0.182
Early AFP response	0.834	0.622
AFP (< 100 ng/dL)	0.756	0.450
DCP (< 1000 mAU/mL)	0.806	0.554
MKI-associated HFSR	0.224	< 0.001	0.241	0.001	0.102-0.567
BCLC B	0.358	0.013	0.404	0.041	0.170-0.964
Hypertension	0.889	0.756
Diarrhea	0.950	0.911
Anorexia	1.671	0.162
Alopecia	0.560	0.177

Early alpha-fetoprotein (AFP) response refers to a ≥ 20% improvement in AFP levels within 2 mo. BCLC: Barcelona Clinic Liver Cancer; DCP: Des-gamma-carboxy prothrombin; MKI-associated HFSR: Multikinase inhibitor-associated hand-foot skin reaction.

Table 4 Univariate and multivariate analyses of variables associated with time to treatment failure

	Univariate analysis		Multivariate analysis
	HR	P value	HR	P value	95%CI
Age (≥ 65 yr)	0.369	0.020	0.475	0.099	0.196-1.150
Initial dose (800 mg)	1.213	0.588
Early AFP response	0.630	0.24
AFP (< 100 ng/dL)	0.988	0.974
DCP (< 1000 mAU/mL)	0.711	0.363
MKI-associated HFSR	0.334	0.004	0.418	0.048	0.175-0.994
BCLC B	0.970	0.932
Hypertension	1.286	0.510
Diarrhea	0.517	0.159
Anorexia	1.652	0.175
Alopecia	0.337	0.019	0.792	0.679	0.262-2.391
Intervention by pharmacists	0.326	0.002	0.425	0.042	0.186-0.971

Early alpha-fetoprotein (AFP) response refers to a ≥ 20% improvement in AFP levels within 2 mo. BCLC: Barcelona Clinic Liver Cancer; DCP: Des-gamma-carboxy prothrombin; MKI-associated HFSR: Multikinase inhibitor-associated hand-foot skin reaction.