Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients

Table 1 Clinical characteristics of the study population at baseline

	Control group	Cooling group	F	Z	P value
Age	51.18 ± 9.27 yr	51.24 ± 10.16 yr	0.863		0.977
Weight	64.20 ± 10.29 kg	65.37 ± 9.74 kg	0.404		0.558
BMI	24.50 ± 3.60 kg/m2	24.98 ± 3.66 kg/m2	0.042		0.503
Height	162 (158-165) cm	162 (160-165) cm		-0.044	0.965
Body surface area	1.6975 (1.6005-1.799) m2	1.723 (1.646-1.802) m2		-0.802	0.423
PLD dose	60 (54.25-60) mg	60 (60-60) mg		-1.53	0.126
Total PLD dose	240 (220-240) mg	240 (240-240) mg		-1.04	0.299
Chemotherapy cycle	4 cycles, 21 d/cycle
Leukocytes	5.66 (4.48-7.0875)	6.02 (4.92-7.47)		-0.971	0.331
Platelets	249.5 (225.5-301.25)	233 (203-270)		-1.96	0.05
Albumin	47.59 (43.375-49.025)	46.5 (44.8-48.424)		-0.194	0.846
Alanine aminotransferase	21 (13.5-33.525)	17 (12.47-24)		-1.502	0.133
Aspartate aminotransferase	21.9 (17-27.5)	20 (17-22.03)		-1.251	0.211
Total bilirubin	12.715 (7.9225-14.9)	10.58 (8.25-13.78)		-1.274	0.203
Creatinine	45.6 (41.465-48.8)	45.4 (42.8-49.5)		-0.234	0.815
Urea Nitrogen	4.69 (4.3-5.1218)	5.1 (4.12-5.9)		-1.485	0.138
Race				-1.400	0.161
Marital status				-0.323	0.747
Profession				-0.999	0.318
Education				-0.467	0.640
Household income level (in recent year)				-0.050	0.960
Resident population (in recent year)				-1.272	0.203
Medical procedures				-0.475	0.635
Whether the patient has hypertension				-0.499	0.618
Whether the patient has diabetes				-0.988	0.323
Whether the patient ever had heart disease				-0.020	0.984
Whether the patient has other tumors				-0.566	0.571
Whether the patient has a long-term medication history				-0.823	0.410
Whether the patient has a smoking history				-1.010	0.313
Whether the patient has a drinking history				0.000	1.000
Whether the patient has the habit of taking health products				-1.036	0.300
Attitude				-1.293	0.196
Character traits				-2.479	0.013
Facing major events in life				-3.258	0.001
Attitude to this matter (suffering from breast cancer)				-2.654	0.008
Whether the patient has undergone surgery				-1.364	0.172
Surgical approach				-0.543	0.587
Chemotherapy administration				-1.344	0.179
Chemotherapy regimen				-1.143	0.253

PLD: Pegylated liposomal doxorubicin; BMI: Body mass index.

Table 2 Intersubjective effect test

	HF-QOL 2nd	HF-QOL 3rd	HF-QOL 4th	GSES 2nd	GSES 3rd	GSES 4th
P1 value	0.621	0.644	0.996	0.781	0.614	0.950
P2 value	0.102	0.677	0.965	0.997	0.704	0.734
P3 value	0.716	0.714	0.900	0.916	0.833	0.701
P4 value	0.443	0.670	0.532	0.850	0.832	0.960

¹The significance level of whether "Character traits" affect the scores.

²The significance level of whether "Facing major events in life" affect the scores.

³The significance level of whether "Attitude to this matter (suffering from breast cancer)" affect the scores.

⁴The significance level of whether the above three affect the scores. HF-QOL: Hand-Foot Skin Reaction and Quality of Life Questionnaire; GSES: General self-efficacy scale.

Table 3 The incidence of hand-foot syndrome, n (%)

	HFS occurrence
	No HFS	Grade 1	Grade 2	Z	P value
Control group	30 (60.0)	19 (38.0)	1 (2.0)	4.686	0.000003
Cooling group	50 (98.0)	1 (2.0)	0 (0.0)

HFS: Hand-foot syndrome.

Table 4 Intra-group comparisons of the general self-efficacy scale score

GSES score		2nd and 1st	3rd and 1st	4th and 1st
Control group	t	-1.982	-2.373	-2.604
	P value	0.053	0.022	0.012
Cooling group	t	-2.047	-2.385	-2.773
	P value	0.046	0.021	0.008

GSES: General self-efficacy scale.

Table 5 Comparison of the general self-efficacy scale score between the two groups

GSES score	1st	2nd	3rd	4th
Control group	19.48 ± 5.88	18.40 ± 5.55	17.52 ± 4.82	17.22 ± 5.16
Cooling group	21.61 ± 6.13	20.67 ± 6.08	19.94 ± 5.81	19.63 ± 6.42
F	0.021	0.479	0.552	1.647
P value	0.078	0.053	0.025	0.041

GSES: General self-efficacy scale.

Table 6 Comparison of the Hand-Foot Skin Reaction and Quality of Life Questionnaire score between the two groups

HF-QOL score	1st	2nd	3rd	4th
Control group	39.14 ± 10.29	21.80 ± 10.10	18.02 ± 5.96	18.08 ± 7.01
Cooling group	39.06 ± 8.56	16.65 ± 10.46	14.22 ± 6.01	14.20 ± 7.39
F	4.559	0.061	0.192	0.025
P value	0.966	0.013	0.002	0.008

HF-QOL: Hand-Foot Skin Reaction and Quality of Life Questionnaire.

Table 7 Intra-group comparisons of the Hand-Foot Skin Reaction and Quality of Life Questionnaire score

HF-QOL score		2nd and 1st	3rd and 1st	4th and 1st
The control group	t	-10.224
	F		20.226	13.952
	P value	0.000	0.000	0.000
The cooling group	t	-14.500
	F		4.781	1.570
	P value	0.000	0.000	0.000

HF-QOL: Hand-Foot Skin Reaction and Quality of Life Questionnaire.

Table 8 Factors that may be related to the occurrence of hand-foot syndrome

Possible risk factors	F	Z	P value
Age	3.354		0.387
BMI	0.088		0.581
Body surface area		-0.649	0.517
Race		-0.2	0.842
Profession		-3.023	0.003
Education		-0.597	0.55
Whether the patient has hypertension		-0.887	0.375
Whether the patient has diabetes		-1.008	0.313
Whether the patient ever had heart disease		-1.04	0.298
Whether the patient has other tumors		-0.896	0.37
Whether the patient has a long-term medication history		-2.083	0.037
Whether the patient has a smoking history		-0.512	0.608
Whether the patient has a drinking history		0	1
Whether the patient has the habit of taking health products		-1.04	0.298
Attitude		-0.363	0.717
Character traits		-1.459	0.145
Facing major events in life		-1.229	0.219
Attitude to this matter (suffering from breast cancer)		-1.26	0.208
Whether the patient has undergone surgery		-0.127	0.899
Surgical approach		-1.137	0.255
Chemotherapy administration		-0.182	0.856
Chemotherapy regimen		-1.398	0.162
Total PDL dose		-0.289	0.773
Leukocytes		-0.816	0.415
Platelets		-1.712	0.087
Albumin		-2.428	0.015
Alanine aminotransferase		-1.177	0.239
Aspartate aminotransferase		-1.517	0.129
Total bilirubin		-0.833	0.405
Creatinine		-0.448	0.654
Urea Nitrogen		-0.088	0.93

PLD: Pegylated liposomal doxorubicin; BMI: Body mass index.

Table 9 Comparison of different cooling methods and the incidence of hand-foot syndrome

n	Tumor	Chemotherapy regimen	Dosage of PLD	Cold therapy equipment	Cooling parts of the body	Cooling time	Incidence of HFS	Ref.
20	Ovarian cancer	Monotherapy	30-50 mg/m2	Ice packs	Around the wrists and ankles	After chemotherapy for 24 h	1/17 (5.9%)	Molpus et al[12]
53	Ovarian cancer	Combination or monotherapy	30-50 mg/m2	Ice packs	Around the wrists and ankles	During chemotherapy infusion	2/28 (7.1%)	Mangili et al[13]
55	Ovarian cancer	Combination	30 mg/m2	FGS	Whole hands and feet	From 15 min before infusion to 15 min after infusion	≥ Grade 2 (31.70%)	Bun et al[14]
41		Monotherapy	50 mg/m2				≥ Grade 2 (5.5%)
51	Breast cancer	Combination	30-35 mg/m2	The cooling patches	Palm and back of hands	Start 15 min before infusion and lasted for 10 h	1/51 (2.0%)	Our study

PLD: Pegylated liposomal doxorubicin.

Table 10 Characteristics of patients with hand-foot syndrome (n=21)

Characteristics	Percentage (%)
Age (yr)
≤ 17	0
18-45	38.1
46-69	61.9
> 70	0
BMI (kg/m2)
Underweight (< 18.5)	0
Normal (18.5-24.9)	42.9
Overweight (25.0-29.9)	52.4
Obese class I (30.0-34.9)	4.8
Obese class II (35.0-39.9)	0
Obese class III (≥40.0)	0
Whether the patient ever had hypertension
Yes	9.5
No	90.5
Whether the patient has diabetes
Yes	4.8
No	95.2
Whether the patient ever had heart disease
Yes	0
No	100
Whether the patient has other tumors
Yes	0
No	100
Whether the patient has a long-term medication history
Yes	9.5
No	90.5
Whether the patient has a smoking history
Yes	0
No	100
Whether the patient has a drinking history
Yes	0
No	100
Whether the patient has the habit of taking health products
Yes	0
No	100
Attitude
Impatient	61.9
Slowcoach	4.8
Somewhere in between	33.3
Character traits
Extroverted	38.1
Introverted	28.6
Somewhere in between	33.3
Facing major events in life
Accept frankly	90.5
Accept after enlightenment	9.5
Difficult to accept after enlightenment and rethinking	0
Attitude to this matter (suffering from breast cancer)
Optimistic	95.2
Slightly optimistic	4.8
Confused	0
Worried	0

BMI: Body mass index.