Effectiveness of Non-Pharmacologic Interventions in Chemotherapy Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Pok-Ja Oh; You Lim Kim

doi:10.4040/jkan.2018.48.2.123

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Oh and Kim: Effectiveness of Non-Pharmacologic Interventions in Chemotherapy Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Review Article

J Korean Acad Nurs 2018;48(2):123-142.

Published online: 15 January 2018

DOI: https://doi.org/10.4040/jkan.2018.48.2.123

Effectiveness of Non-Pharmacologic Interventions in Chemotherapy Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Pok-Ja Oh¹, You Lim Kim^2,

¹Department of Nursing, Sahmyook University, Seoul

²Department of Physical Therapy · Laboratory of Rehabilitation & Health Science, Sahmyook University, Seoul, Korea

Address reprint requests to : Kim, You Lim Department of Physical Therapy · Laboratory of Rehabilitation & Health Science, Sahmyook University, 815 Hwarang-ro, Seoul 01795, Korea Tel: +82-2-3399-1589 Fax: +82-2-3399-1954 E-mail: youlimy81@naver.com

Received 14 November 2017 Revised 12 March 2018 Accepted 14 March 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution NoDerivs License. (http://creativecommons.org/licenses/by-nd/4.0) If the original work is properly cited and retained without any modification or reproduction, it can be used and re-distributed in any format and medium.

Abstract

Purpose

This study was conducted to evaluate the effectiveness of non-pharmacologic interventions in chemotherapy-induced peripheral neuropathy (CIPN).

Methods

PubMed, Cochrane Library CENTRAL, EMBASE, CINAHL, and several Korean databases (Until August 2017) were searched. The main search strategy combined terms for peripheral neuropathy and presence of neoplasms. The risk of bias was assessed using the Cochrane's Risk of Bias tool for randomized studies and the Risk of Bias Assessment tool for non-randomized studies. To estimate the effect size, a meta-analysis of the studies was performed using the Rev Man 5.3 program of the Cochrane Library random-effects models were used in the analyses.

Results

Twenty-two studies with a total of 954 participants met the inclusion criteria. Of the 22 studies, 12 were used to estimate the effect size of the non-pharmacologic interventions. The non-pharmacologic interventions used in patients with CIPN were exercise, acupuncture, massage, and foot bath. The acupuncture significantly reduced CIPN symptoms and signs (d=-0.71) and CIPN pain (d=-0.73) (p<.001). Massage and foot bath were also effective in reducing CIPN symptoms (d=-0.68; 95% CI=-1.05, -0.30; p<.001; I²=19%).Exercis-es were effective in improving muscle strength and endurance(d=-0.55) and quality of life (d=-2.96), but they were not significantly effective in improving CIPN.

Conclusion

Although these results provide little evidence of the effectiveness of acupuncture, massage, and foot bath in the treatment of CIPN, they suggest that these interventions can reduce CIPN symptoms in patients with cancer. However, the findings of this study should be interpreted with caution as there is a relative lack of data in this field, and additional well-designed studies are needed. PROSPERO registration: CRD42017076278.

Keywords: Chemotherapy, Adjuvant, Meta-analysis, Peripheral Nervous System Diseases

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Figure 1.

Flow diagram of study screening.

Figure 2.

Forest plots of the effect of non-pharmacologic intervention.

Figure 3.

Funnel plots of standard error by standardized mean difference.

Table 1.

Descriptive Summary of Included Studies

Study	Design/Sample characteristics	Intervention	Outcomes (Scale)	Results
		Exercise
Mols et al.,	Population-based survey of	Type: Physical Activity (walking,	1) QOL (EORTC QLQ-C30)	1) Physical activity was
2015	colorectal cancer survivors:	bicycling, gardening,	2) Chemotherapy-induced	associated with less CIPN-
(Netherland)	chemotherapy (n=506) vs.	housekeeping, and sports	peripheral neuropathy	like symptoms and a higher
	no chemotherapy (n=1137)	participation)	(EORTC QLQ-CIPN20)	QOL
	groups	Format (setting): Individual (home)	3) Physical Activity
	Chemotherapy: Yes	Providers: Self	Questionnaire (EPIC)
	Mean age (years):	Session: <150 min/week or ≥150
	Chemotherapy group	min/week (Physical activity
	(66.7), no chemotherapy	guideline)
	group (70.6)
Schwenk		Type: Interactive game-based	1) CIPN -Severity (VPT score)	1-3) No difference compared
et al., 2016	RCT (pilot study) in older	balance training	− Pain (NRS)	to baseline
(USA)	cancer patients undergoing	Format (setting): Individual (cancer	− Numbness in feet (NRS)	4) Improved postural balance
	chemotherapy: CIPN	center clinic)	2) Health related QOL (SF-
	(n=22), experimental	Providers: Supervisor (computer	12)
	(n=11), and control (n=11)	based training)	3) Fear of falling (FES-I)
	groups	Session: 45 min/session,	4) Balance (Feet closed-EO,
	Chemotherapy: Yes	2 times/week for 4 weeks	EC, semi-tandem-EO)
	Mean age (years): 70±8.7
Henke et al.,	RCT in patients with	Type: Strength and endurance	1) ADL (Barthel Index)	1) Increased ADL
2014 (USA)	stages Ⅲ-Ⅳ lung cancer	training	2) QOL (EORTC QLQ-C30)	2) Increased QOL
	undergoing chemotherapy:	Format (setting): Individual	3) Peripheral neuropathy	3) Improved peripheral
	CIPN (n=29), experimental	(hospital)	(EORTC QLQ -13)	neuropathy
	(n=18) and control (n=11)	Providers: Supervision of a licensed	4) Functional capacity (6	4) Increased functional
	groups	physiotherapist	MWT, staircase walking)	capacity
	Platinum-based	Session: 1) Strength training with	5) Muscle strength (curl-up	5) Improved strength
	chemotherapy	elastic band:	test)
	Mean age: older than 18	3 sessions, 2-3 times/week during
	years	3 cycles of chemotherapy
		2) Endurance training
		− Staircase walking: 2 min,
		5 times/week during 3 cycles
		of chemotherapy
		− 6-MWT: 6 min walking,
		5 times/week during 3 cycles
		of chemotherapy
Tofthagen	Single-group clinical trial in	Type: Exercise	1) Muscle strength	1) Improved balance
et al., 2014	colorectal cancer survivors	Format (setting): Group	(handheld isokinetic	2) Improved strength
(USA)	undergoing chemotherapy:	(community)	dynamometer)	3) Reduced neuropathic
	CIPN (n=3)	Providers: Physical therapist	2) Balance (postural	symptoms
	Chemotherapy: Oxaliplatin	Session: Strength training:	instability, unipedal stance	e
	Mean age (years): 69	20 min/session, 2 times/week	time, TUG, mCTSIB, DGI)
		for 12 weeks	3) Peripheral neuropathy
		stretching: 10~15 min/session,	(CIPNAT, TNSr)
		2 times/week
		Balance training: 30 min/session,
		2 times/week
Wonders,	Single-group clinical trial in	Type: Supervised individualized	1) QOL (McGill)	1) Improved QOL
2014 (USA)	cancer patients undergoing	exercise program	2) CIPN symptom (LANSS)	2) Decreased Symptom of
	chemotherapy: CIPN (n=38)	Format (setting): Individualized	3) Fitness evaluation	CIPN
	Chemotherapy: Taxanes and	(medical center)	– Flexibility (Lafayette	3) Improved in VO₂max,
	vinorelbine	Providers: Certified cancer exercise	Tester)	muscular endurance and
	Mean age (years): male	specialist	− Muscular endurance/	flexibility
	(62.3±2.5), female (57.4±	Session: 20~30 min/session,	strength (curl up test)
	4.2)	2 times/week for 12 weeks	− Submaximal VO₂max
			(Bruce treadmill test)
Wonders	Single-group clinical trial	Type: Home-based exercise	1) Step (Pedometer)	1) Less of unpleasant skin
et al., 2013	in breast cancer patients	(resistance exercise & walking)	2) QOL (McGill)	sensations, abnormally
(USA)	undergoing chemotherapy	Format (setting): Individual (home)	3) Pain (Leeds Assessment	sensitive to touch and
	(n=14).	Providers: Kinesiologist	of Neuropathic Symptoms	sudden bursts (p=0.05).
	Chemotherapy: Taxanes and	Session: walking: 10~30 min/	and Sign)	2) Significantly improved of
	vinorelbine	session, 2~5 times/wk for 10 wks		QOL
	Mean age (years): 51.6±2.6	Resistance exercises: 3 times/week
		for 10 weeks.
Streckmann	RCT in lymphoma patients	Type: Aerobic endurance and	Primary: QOL (EORTC	1) Improved QOL
et al., 2014	undergoing chemotherapy:	strength training, Sensorimotor	QLQ-C30)	2) Reduced symptoms of PNP-
(USA)	experimental group (n=30)	training	Secondary:	related deep sensitivity
	and control group (n=31)	Format (setting): Individual (medical	1) Peripheral deep sensitivity	3) Improved balance control
	Chemotherapy: Yes	center)	(tuning fork)	on static and dynamic
	Mean age(years): Exp. (44),	Providers: Certified or	2) Activity level (MET)	surface
	Cont. (48)	physiotherapist	3) Balance control (stable
		Session: 2 times/week for 36 weeks	force plate/foam pad)
		1) Aerobic endurance training:	4) Side-effects monitored:
		10~30 min walk on treadmill	nutrition statue, anxiety
		2) Sensorimotor training: 20-s	and depression (HADS)
		intervals, 1 min between exercise
		3) Strength training: 1 min at
		maximum force with hera-Band^TM
		Acupuncture
Valentine-	Retrospective case series	Type: Acupuncture (Acupoints:	CIPN grade (CTCAE)	Improved the symptoms of
Davis. 2015	of colorectal cancer	individual basis)		CIPN
(USA)	patients who underwent	Format (setting): Individual
	chemotherapy with	(hospital)
	gradeⅠ–ⅣCIPN (n=10)	Providers: Unclear
	Chemotherapy: Oxaliplatin	Session: 20 min, 2∼21 sessions
	Mean age (years): 53.1
Bao et al.,	Single-arm pilot studyin	Type: Acupuncture	Signs and symptoms of	Decreased pain and improved
2014 (USA)	multiple myeloma patients	Format (setting): Individual	neuropathy:	function (walking, hand
	undergoing chemotherapy:	(hospital)	1) TNSc	function: buttoning buttons,
	gradeⅡCIPN (n=27)	Providers: Experienced	2) FACT/GOG-NTx	trouble feeling objects)
	Chemotherapy: Bortezomib	acupuncturist	3) NPS
	Mean age (years): 63 (49–77)	Session: 20 min, 10 sessions for
		10 weeks
Garcia et al.,	Single-arm pilot study in	Type: Electroacupuncture	1) Peripheral neuropathy	1) Reductions in pain
2014 (USA)	) multiple myeloma patients	Format (setting): Individual	(FACT/GOG-Ntx)	2) Improvements in FACT/
	undergoing chemotherapy:	(hospital)	2) QOL (FACT-G survey)	GOG/Ntx scores
	CIPN (n=19)	Providers: Two licensed	3) Pain (Brief Pain Inventory-	3) Improvements in function
	Chemotherapy: Bortezomib	acupuncturists with over 30 years’	Short Form)	tests
	and thalidomide	experience	4) Function tests (coin test,
	Mean age (years): 64	Session: 20 min, 2~3 treatments/	button test, walking and
		week, 20 sessions for 9 weeks	postural stability/fall risk)
Han et al.,	Single-group clinical trial in	Type: Acupuncture	1) CIPN grade (CTCAE) and	1) Reductions in CIPN pain
2014	patients with myeloma or	Format (setting): Individual	pain (VAS)	2) Improvements in QOL
(Korea)	lymphoma undergoing	(hospital)	2) QOL (FACT/GOG-Ntx)
	chemotherapy: gradeⅡCIPN	Providers: Doctor of oriental	3) CIPN (FACT/GOG-Ntx)
	(n=5)	medicine
	Chemotherapy: Bortezomib	Session: 15 min, 3 times/week
	and thalidomide	during 3 weeks
	Mean age (years): 67.8±7.29
Lee et al.,	Case report of a patient	Type: Acupuncture	1) CIPN grade (CTCAE)	1) Reductions in CIPN grade
2014	with colorectal cancer	Format (setting): Individual	2) CIPN (EORTC QLQ-	and pain
(Korea)	whounderwent	(hospital)	CIPN20)	2) Improvements in QOL
	chemotherapy: CIPN (n=1)	Providers: Doctor of Oriental	2) QOL (EORTC QLQ-C30)
	Chemotherapy: Oxaliplatin	medicine
	Mean age (years): 47	Session: 20 min, one time/week,
		15 sessions
Park et al.,	Case report of a patient	Type: Electroacupuncture	1) CIPN grade (patient	1) Reductions in CIPN pain
2015	with breast cancer who	Format (setting): Individual	neurotoxicity	2) Improvements in CIPN
(Korea)	underwent chemotherapy:	(hospital)	questionnaire)	grade
	CIPN (n=1)	Providers: Doctor of Oriental	2) Pain (VAS)
	Chemotherapy: Docetaxel	medicine
	Age(years): 56	Session: 20 min, 2 times/day during
		2 weeks
Ogawa	Single-arm pilot studyin	Type: Acupuncture (contact needle	1) CIPN symptoms (CTCAE),	1) Improved the symptoms of
et al., 2013	patients with colorectal and	therapy: Traditional Japanese	FACT/GOG-Ntx	CIPN
(Japan)	breast cancer undergoing	methods of acupuncture)
	chemotherapy (n=4)	Format (setting): Individual
	and who had undergone	(hospital)
	chemotherapy (n=2) with	Providers: Senior acupuncturist
	grade I–II CIPN	Session: 30~60 sec/session, 4~6
	Chemotherapy: Taxanes and	treatments for 3 months
	oxaliplatin
	Mean age (years): 64.3
Rostock	Four-arm RCT in	Type: Electroacupuncture (EA) or	1) CIPN complaints (Detailed	1) No improvement inthe
et al., 2013	cancer patientswith	Hydroelectric bath (HB) or vitamin	questionnaires)	symptoms of CIPN
(Germany)	CIPNundergoing:	B1 and B6 (vitamin B) vs. placebo	2) Neuropathic symptoms	2) No improvement in QOL
	experimental group (n=42)	Format (setting): Individual	(NRS, Neuropathy score,
	and control group (n=17)	(hospital)	Electroneurographical
	Chemotherapy: Taxanes and	Providers: Two trained physicians	test)
	platinum derivatives	Session: 15 min, 8±1 sessions for 3	3) QOL (EORTC QLQ-C30)
	Mean age (years): Exp. (EA:	weeks
	49.9±9.6, Con. (52.0±8.1)
Donald et al.,	Retrospective service	Type: Acupuncture	1) CIPN symptom (evaluation	n 1) Improvement in PN
2011 (UK)	evaluation of cancer	Format (setting): Individual	form)	symptoms
	patients who underwent	(outpatient clinic)	2) Additional acupuncture	2) Reduction in analgesic use
	chemotherapy: CIPN (n=18)	) Providers: Qualified nurses	benefits	and improved sleeping
	Chemotherapy: Bortezomib,	Session: 30~45 min/session, 6		patterns.
	thalidomide, taxanes and	treatments for 6weeks
	platinum derivatives
	Mean age (years):
	51.83±12.97
Schroeder	NRCT (pilot study) in	Type: Acupuncture (traditional	1) Nerve conduction velocity	1) Improved the symptoms of
et al., 2011	cancer patients with CIPN	Chinese medicine)	(nerve conduction study)	PN
(Germany)	undergoing chemotherapy:	Format (setting): Individual
	experimental group (n=6)	(hospital)
	and control group (n=5)	Providers: Senior physician who had
	Chemotherapy: Taxanes and	received >1000 h of acupuncture
	platinum derivatives	training
	Mean age (years):Exp. (64),	Session: 20 min/session, 10
	Con. (65)	treatments for 3months
Wong &	Case series of gynecological	Type: Acupuncture	1) Pain	1) Improvements in sensation
Sagar, 2006	cancer patients who	Format (setting): Individual	2) Physical assessment	gait, and balance
(Canada)	underwent with gradeⅡ–	(hospital)	(sensation, gait, and	2) Decreased analgesic dosage
	ⅢCIPN (n=5)	Providers: Certified therapist in	balance)	and symptoms (pain,
	Chemotherapy: Carboplatin	medical acupuncture		numbness and tingling)
	(total, 3500 mg) and	Session: First: 30~45 min/session,
	paclitaxel (total, 1860 mg)	once a week for 12 weeks
	Age: 60~71 years
		Massage / Foot bath
Noh 2017	RCT in patients with	Type: Self-foot reflexology	1) CIPN symptoms and	1) Decreased CIPN symptoms
(Korea)	gynecologic cancer	Format (setting): Individual	interference (CIPNAT)	andinterference
	undergoing chemotherapy:	(hospital andhome)	2) Peripheral skin	2) Increased peripheral skin
	experimental group (n=32)	Providers: Nurse (certified foot	temperature	temperature
	and control group (n=31)	reflexology)	3) Anxiety and depression	3) Reduced anxiety and
	Chemotherapy: Taxane	Session: 20 min/session, 3 times/	(HADS)	depression
	andplatinum	week for 6 weeks
	Mean age (years): Exp.
	(56.34±9.04), Con.
	(55.36±9.96)
Lee et al.,	NRCT in patients with	Type: Foot reflexology	1) CIPN (EORTC QLQ-	1) Less peripheral neuropathy
2012	various cancer types	Format (setting): Individual	CIPN20)	and symptom distress
(Korea)	undergoing chemotherapy:	(hospital and home)	2) Pain (VAS)	2) No difference in anxiety
	experimental group (n=14)	Providers: Nurse (certified foot	3) Symptom distress (Distress	s and depression
	and control group (n=17)	reflexology)	Thermometer)
	Chemotherapy: Oxaliplatin	Session: 20 min/session, 5 times/	4) Anxiety and depression
	Mean age (years): Exp. (59.9±	± week for 4 weeks	(HADS)
	8.12), Con. (57.7± 8.88)
Cunningham	Case report ofesophageal	Type: Manual therapy (therapeutic	1) MD Anderson Symptom	1) CIPN symptoms reduced to
et al., 2011	patient at stage III who	massage)	Inventory	grade I
(USA)	underwent chemotherapy	Format (setting): Individual	2) Micromuscular blood flow	2) Increased temperature in
	with grade ⅡCIPN (n=1)	(massage therapy room)	(Infrared thermometry)	each extremity
	Chemotherapy: Docetaxel	Providers: Two licensed massage
	and cisplatin	therapist
	Age: 45 years	Session: 25 min/session, 3 times
		/week for 6 weeks
Kim, 2017	NRCT of patients with	Type: Foot bath therapy	1) CIPN symptom and pain	1) CIPN symptom and pain
(Korea)	various cancer types who	Format (setting): Individual	2) CIPN interference	partially supported
	underwent chemotherapy	(hospital)		2) CIPN interference partially
	with experimental (n=11)	Providers: Nurse		supported
	and control (n=13) groups	Session: 25 min/session, 4 times
	Chemotherapy: Yes	/week for 2 weeks, 11 sessions
	Mean age (years): Exp.
	(44.55±10.25), Con.
	(49.77±8.14)

MWT=The 6-minute walk test; ADL=Activities of daily living; CIPN=Chemotherapy induced peripheral neuropathy; CIPNAT=Chemotherapy nduced peripheral neuropathy assessment tool; Cont.=Control group; CTCAE=Common terminology criteria for adverse events; DGI=Dynamic ait index; EC=Eyes closed; EO=Eyes opened; EORTC-QLQ=EORTC-QLQ=European organization for research and treatment of cancer quality-f-life questionnaire; EPIC=European prospective investigation into cancer; Exp.=Experimental group; FACT/GOG-NTx=Functional assessment f cancer therapy/gynecological oncology group-neurotoxicity; FACT-G=Functional assessment of cancer therapy-general; FES-I=Falls efficacy cale international; HADS=Hospital anxiety and depression scale; LANSS=Leeds assessment of neuropathic symptoms and sign; mCTSIB=modified linical test for sensory interaction in balance; MET=Metabolic equivalent; Min=Minute, NPS=Neuropathy pain scale; NRCT=Non-Randomized ontrolled trial; NRS=Neuropathic symptoms on numerical rating scale; PN=Peripheral neuropathy; PNP=Peripheral neuropathy; QOL=Quality of life; CT=Randomized clinical trial; SF-12=Short-Form Health Survey-12; TNSc=Clinical total neuropathy score; TNSr=Total neuropathy score reduced; UG=Timed up and go; VAS=Visual analog scale; VO₂max=Maximal oxygen consumption; VPT=Vibration perception threshold.

Table 2.

Descriptive Summary of Included Studies (N=22)

Characteristics		Categories	n (%) or Mean
General	Year	<2010	1 (4.5)
		2011~2013	8 (36.4)
		2014~2016	11 (50.0)
		>2017	2 (9.1)
	Country	USA	10 (45.4)
		Germany	2 (9.1)
		Korea	6 (27.3)
		Other countries (UK, Canada, Japan)	4 (18.2)
	Study design	RCT	5 (22.7)
		Non-RCT	3 (13.7)
		Single-group clinical trial	8 (36.4)
		Case report	5 (22.7)
		Cross-sectional study	1 (4.5)
Participants	Sample size: cross-sectional	506	1(4.5)
	Sample size: clinical trial	<10	8 (36.4)
	(Range=1∼61, mean=21.33,	11~20	4 (18.2)
	total= 448)	>21	9 (40.9)
	Age (year)	<50	4 (18.2)
	(Mean=55.81)	51~60	8 (36.4)
		>61	9 (40.9)
		Unclear	1 (4.5)
	Cancer type	Colorectal cancer	4 (18.2)
		Breast cancer	2 (9.1)
		Mixed cancers	8 (36.4)
		Multiple myeloma	3 (13.6)
		Other cancer (lung, gynecological)	5 (22.7)
	Chemotherapy agents	Taxanes	6 (24.0)
		Platinum-based	6 (24.0)
		Bortezomib/Thalidomide	3 (12.0)
		Combination	6 (24.0)
		Unclear	4 (16.0)
Intervention	Type	Exercise	7 (31.8)
		Acupuncture	11 (50.0)
		Massage	4 (18.2)
	Setting	Home/Community	2 (9.1)
		Hospital/Clinic	16 (72.7)
		Home+hospital	4 (18.2)
	Providers	Physician	5 (22.7)
		Nurse	4 (18.2)
		Physical therapist	4 (18.2)
		Kinesiologist	2 (9.1)
		Acupuncturist	4 (18.2)
		Self/Unclear	3 (13.6)
	Duration (mean)	Exercise	22.33 min/session,
			2.75 times/week for
			12.83 weeks
		Acupuncture	20.95 min/session,
			4.3 times/week for 8.4 weeks
		Massage	22.50 min/session,
			3.75 times/week for 4.5 weeks
Outcome &	Chemotherapy-induced peripheral	• Symptom:
Measurement*	neuropathy (symptom, pain, grade)	EORTC QLQ-CIPN20	3 (20.0)
		NRS	2 (13.3)
		EORTC QLQ-13	1 (6.6)
		CIPNAT	3 (20.0)
		TNSr/TNSc	2 (13.3)
		FACT/GOG-NTx	3 (20.0)
		MD Anderson Symptom Inventory	1 (6.6)
		• Pain:
		LANSS	2 (22.2)
		NPS/VAS/Brief Pain Inventory	7 (77.8)
		• Grade;
		CTCAE	4 (57.1)
	Quality of life	EORTC-QLQ-C30	5 (50.0)
		FACT-G	2 (20.0)
		SF-12	1 (10.0)
		McGill	2 (20.0)
	Physical activity	EPIC (Questionnaire)	1 (25.0)
		MET	1 (25.0)
		Pedometer	1 (25.0)
		Coin test, button test	1 (25.0)
	Balance	Feet closed-EO, EC/Semi-tandem-EO	1 (25.0)
		Postural instability/Unipedal stance time/	1 (25.0)
		TUG/ mCTSIB/DGI
		Stable force plate/foam pad	1 (25.0)
		Fall risk	1 (25.0)
	Muscle strength & endurance	Curl up test	2 (33.3)
		6MWT	2 (33.3)
		Staircase walking	1 (16.7)
		Pedometer	1 (16.7)

6MWT=The 6-minute walk Test; CIPNAT=Chemotherapy induced peripheral neuropathy assessment tool; CTCAE=Common terminology criteria for adverse events; DGI=Dynamic gait index; EC=eye close; EO=eye open; EORTC-QLQ=European organization for research and treatment of cancer quality-of-life questionnaire; EPIC=European prospective investigation into cancer; FACT/GOG-NTx=Functional assessment of cancer therapy/ gynecological oncology group-neurotoxicity; FACT-G=Functional assessment of cancer therapy-general; LANSS=Leeds assessment of neuropathic symptoms and sign; mCTSIB=Modified Clinical test for sensory interaction in balancem; MET=Metabolic equivalent; Min=minute, NPS=Neuropathy pain scale; NRS=Neuropatic symptoms on numerical rating scale; PN= peripheral neuropathy; PNP=peripheral neuropathy; QOL=Quality of life; RCT=Randomized clinical trial; SF-12=Short-Form Health Survey-12; TNSc=Clinical total neuropathy score; TNSr=Total neuropathy score reduced; TUG=Timed up and go; VO₂max=maximal oxygen consumption; VAS=Visual analog scale.

^*Multiple responses.

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