Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx

Contents lists available at ScienceDirect

Critical Reviews in Oncology / Hematology

journal homepage: www.elsevier.com/locate/critrevonc

Effects of exercise on cancer patients suffering chemotherapy-induced

peripheral neuropathy undergoing treatment: A systematic review
Federica Duregona, Barbara Vendramina, Valentina Bulloa, Stefano Gobboa, Lucia Cugusib,
⁎
Andrea Di Blasioc, Daniel Neunhaeuserera, Marco Zaccariaa, Marco Bergamina, , Andrea Ermolaoa
a
Sport and Exercise Medicine Division, Department of Medicine, University of Padova, Italy
b
Department of Medical Sciences ‘M. Aresu’, University of Cagliari, Cagliari, Italy
c
Department of Medicine and Aging Sciences ‘G. d’Annunzio’, University of Chieti-Pescara, Italy

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and
CIPN clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been
Balance control done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms.
Quality of life Objective: This document aims to summarize and analyze systematically the current body of evidence about the
Physical exercise
effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in
Undergoing chemotherapy
Review
patients with CIPN.
Literature survey: Specific terms were identified for the literature research in MEDLINE, Scopus, Bandolier,
PEDro, and Web of Science.
Methodology: Five manuscripts were considered eligible for this review. Quality appraisal distinguished two
studies as high quality investigations while three with low quality. Results were summarized in the following
domains: “CIPN symptoms”, “Static balance control”, “Dynamic balance control”, “Quality of life and Physical
function”.
Synthesis: Significant improvements were detected on postural control. Additionally, patients’ quality of life and
independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance,
strength and sensorimotor training showed larger improvements.
Conclusions: This systematic review comes from a highly selected but small source of data. Nevertheless, specific
exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these
interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the lim-
itations due to chemotherapy.

1. Introduction
In the past decades, there was an increase of cancer-survivors and
prevalence rates resulting from the development of novel treatments
and improved diagnostic methods. Nevertheless, chemotherapeutic
treatments are continuing to induce by itself a huge number of long-
term side effects, that can be highly detrimental for both physiological
and psychological patients’ health (Derksen et al., 2017). Besides phy-
sical damages, there are specific decreases in the quality of life and
patients often encounter limitations in the neuromuscular function
(Niederer et al., 2014). Within this clinical framework, in cancer pa-
tients Peripheral Neuropathy (PNP) plays a pivotal role since it is the
most common neurological and clinically relevant side effect
(Streckmann et al., 2014a) of many commonly used chemotherapeutic
agents such as taxanes (paclitaxel) (Song et al., 2017), bortezomib, le-
nalidomide, vinca-alkaloids (vinorelbine) (Wolf et al., 2008), and pla-
tinum-based antineoplastic (Kerckhove et al., 2017). The incidence of
Chemotherapy-Induced Peripheral Neuropathy (CIPN) can be variable,
ranging from 30% to 60% on patients treated with neurotoxic che-
motherapy (Seretny et al., 2014), and it can affect both youth and el-
derly subjects. There are several factors that can influence the in-
cidence, such as the dose intensity, the cumulative dose, the therapy
duration, the co-administration of other neurotoxic chemotherapy
agents and the potential pre-existing conditions, for example diabetes
and alcohol abuse (Kannarkat et al., 2007; Quasthoff and Hartung,
2002; Windebank and Grisold, 2008). Also, patients with CIPN gen-
erally suffer from a variety of symptoms including: pain, muscle
weakness, reduced balance control, insecure gait, reduced or absent

⁎
Corresponding author at: Sport and Exercise Medicine Division, Department of Medicine, University of Padova, Italy.
E-mail address: marco.bergamin@unipd.it (M. Bergamin).

https://doi.org/10.1016/j.critrevonc.2017.11.002
Received 19 December 2016; Received in revised form 12 October 2017; Accepted 5 November 2017
1040-8428/ © 2017 Elsevier B.V. All rights reserved.

Please cite this article as: Duregon, F., Critical Reviews in Oncology / Hematology (2017), https://doi.org/10.1016/j.critrevonc.2017.11.002
F. Duregon et al.
reflexes (Streckmann et al., 2014a). They also present an altered sen-
sation (numbness, burning, tingling, etc.) (Streckmann et al., 2014a),
with dysesthesias and paresthesias in a stocking and glove pattern
(Wampler et al., 2007), commonly located in lower and upper ex-
tremities. These symptoms may be resolved but a complete resolution is
rare; indeed, in a large number of cases it is not reversible at all, as
indicated by Quasthoff and Colleagues (Quasthoff and Hartung, 2002).
For these reasons, motor deficits including balance impairment,
lower gait speed and lower limb strength are also recurring, with an
increased falling frequency (Niederer et al., 2014). Moreover, the pos-
tural control shows clinical meaningful impairments, and as a vicious
circle, gait speed is also negatively affected due to a decrease in phy-
sical exercise participation with a framework of general physical de-
conditioning. These deficits, associated with an increased fear of falling,
may limit patients’ independence (Schwenk et al., 2016). In addition,
the neuropathy often interferes with the daily activities leading to se-
vere impairments of the patient’s quality of life (QOL) (Izycki et al.,
2016). From these perspectives, on the other side, it can be supposed
that an improvement of quality of life, due to physical active lifestyle, in
turn, could enhance the overall physical function, the postural control,
and promotes a reduction in the risk for falls (Bullo et al., 2015). Fur-
thermore, CIPN has become a crucial limiting factor for therapy,
causing treatment delays, dose reductions, or even discontinuation of
therapy, which can affect the outcome and compromise survival rates
(Stubblefield et al., 2009).
Nowadays, research has mainly focused on pharmacological thera-
pies, whereas little effort has been done to investigate the potentially
beneficial effects of specific exercises to counteract the described
symptoms (Streckmann et al., 2014a). In a summary document of
Streckmann et al. (2014a), the effects of exercise were evaluated in
different disease conditions; in particular, protocols included type II
diabetic patients, one study on cancer patients and six about other
diseases. In general line, these trials have shown that exercise can re-
duce motor deficits induced by Peripheral Neuropathy and can ame-
liorate coordination, preventing muscle loss with an adequate dose of
strength training, also improving related neuromuscular parameters
(Streckmann et al., 2014a). More specifically, other several improve-
ments were found in Diabetic Peripheral Neuropathy (DPN), that is a
frequent encountered form of PNP (Landowski et al., 2016). About the
type of exercise, it has been shown that long-term, supervised aerobic
training could prevent the onset or modify the natural history of DPN
(Balducci et al., 2006). Also, an intense exercise regimen, designed to
enhance distal lower extremity strength, has been able to improve
tandem stance, functional reach, and unipedal stance, three important
outcome measures of balance control (Richardson et al., 2001).
At the base of these statements, the aim of this systematic review is
to summarize and analyze the current body of evidence about the ef-
fects of specific exercise protocols on CIPN symptoms, balance control,
physical function and quality of life in patients with CIPN.
2. Materials and methods
2.1. Study design
This is a systematic review of the literature with the aim to analyze
all studies that investigate the effects of physical exercise protocols on
the physical function, balance control, quality of life (QOL), and the
reduction of CIPN symptoms, only including investigations with cancer
patients undergoing chemotherapy.
2.2. Literature search
The methodological search was carried out in September 2017 and
was performed through the online databases: MEDLINE, Scopus,
Bandolier, PEDro and Web of Science. Keywords “Chemotherapy”,
“Induced”, “Peripheral”, “Neuropathy” were entered in the systematic
2
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
search, associated with “postural control”, “balance control”, “physical
activity”, “physical exercise”, “proprioception”, “equilibrium” and
“stability”. In addition, references were examined in each eligible ar-
ticle and further relevant manuscripts were screened when a positive
match was observed.
2.3. Inclusion and exclusion criteria
Studies considered for this review had to include a physical exercise
intervention with at least a quality of life or a balance evaluation,
preferably with a structured exercise protocol tailored for cancer pa-
tients undergoing treatment with diagnosed CIPN. Only original
manuscripts published in indexed and peer-review journals and written
in English language were considered. Further inclusion criteria required
pre- and post-intervention comparisons, one or both genders from all
races, in all ages, and with whatever diagnosis of cancer. Cross-sec-
tional studies, case reports, published abstracts, dissertation materials,
and conference presentations were not included.
2.4. Study quality assessment
The quality of the studies was assessed through the adapted nine
criteria checklist provided by the Cochrane Collaboration Back Review
Group (van Tulder et al., 1997). As in previous reviews, the checklist
had to be marginally adapted to rate the strength of the evidence (Bullo
et al., 2015; Bergamin et al., 2012; Gobbo et al., 2014). Each study in
the review was scored based on the following nine criteria: (1) ‘Was the
method of randomization adequate?’; (2) ‘Were the groups similar at
baseline regarding the outcome measures?’; (3) ‘Were inclusion and
exclusion criteria adequately specified?’; (4) ‘Was the drop-out rate
described adequately?’; (5) ‘Were all randomized participants analyzed
in the group to which they were allocated?’; (6) ‘Was the compliance
reported for all groups?’; (7) ‘Was Intention-to-treat analysis per-
formed?’; (8) ‘Was the timing of the outcome assessment similar in all
groups?’; (9) ‘Was a follow-up performed?’. When the study provided a
satisfactory description, a positive value was assigned (+). If the cri-
terion description was considered absent, unclear, or lacked the speci-
fied content, a negative value was assigned (−). A study was qualita-
tively estimated as high quality if it showed a positive score on five to
nine of the criteria; otherwise, it was considered a low quality study
(van Tulder et al., 1997).
2.5. Data extraction and synthesis
Two researchers independently examined all abstracts of the
sourced studies. Full manuscripts were then analyzed in more detail to
determine whether they met eligibility criteria. Each researcher per-
formed a final quality check on each study. Afterwards, the individual
searches were combined, compared, and reviewed for applicability, and
a consensus was made regarding their inclusion in the study. In case of
discrepancies, the review process was repeated and a third researcher
was consulted. Quality assessment using the modified Cochrane meth-
odological quality criteria was then independently applied and dis-
cussed before final appointment of the quality score.
Several domains were identified for the categorization of study
outcomes. In particular, results were
classified to “CIPN symptoms”, “Static balance control”, “Dynamic
balance control”, “Quality of life and Physical function”.
3. Results
3.1. Description of the studies
A total of 2221 studies resulted from the literature search. Firstly
duplicates were removed, then 1318 records were screened. Applying
inclusion and exclusion criteria, 5 studies (Schwenk et al., 2016;
F. Duregon et al.
Fig. 1. Flow chart of the literature research.
Streckmann et al., 2014b; Wonders et al., 2013; Mizrahi et al., 2015;
Fernandes and Kumar, 2016) were considered eligible for this review
(Fig. 1). Three manuscripts were classified as CIPN supervised-training
interventions (Schwenk et al., 2016; Streckmann et al., 2014b;
Fernandes and Kumar, 2016), and two were classified as CIPN home-
based intervention (Wonders et al., 2013; Mizrahi et al., 2015), all of
them with pre- and post-intervention evaluations. Sample sizes ranged
from 14 to 56 subjects; participants were mostly female (57%), with an
average of 54.7 years old. At baseline, a total of 147 subjects were re-
cruited and 122 patients successfully completed the exercise program,
including the post-intervention assessment (25 dropouts were re-
ported). All subjects had a diagnosis of malignancy; in three studies,
100% of the participants received chemotherapy during the exercise
intervention (Streckmann et al., 2014b; Mizrahi et al., 2015; Fernandes
and Kumar, 2016), in the other two, 54% (Schwenk et al., 2016) and
57% (Wonders et al., 2013) of subjects were currently taking the
treatment. Different exercise training interventions were administered;
in general, exercise programs were structured by an aerobic training
(walking or cycling exercises were performed from 55% to 80% of
maximum heart rate), and by a strength training with elastic bands
3
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
(different resistance exercises executed with Thera-Band) and ca-
listhenics (performed from 50% to 70% of one maximum repetition).
Two manuscripts incorporated a core stability and sensorimotor
training (Streckmann et al., 2014b; Mizrahi et al., 2015); finally, two
studies focused on a specific balance training 2(Schwenk et al., 2016;
Fernandes and Kumar, 2016). Mainly, single session lasted from 30 to
60 min, while protocols were performed from two to five times per
week. Durations of interventions were from 3 to 36 weeks.
Quality appraisal classified two studies as high-quality investiga-
tions (Schwenk et al., 2016; Streckmann et al., 2014b), while three as
low quality (Wonders et al., 2013; Mizrahi et al., 2015; Fernandes and
Kumar, 2016) (Table 1). From a methodological prospective, rando-
mization was applied in two studies (Schwenk et al., 2016; Streckmann
et al., 2014b), both showed similarity of the groups’ participants at
baseline. All studies adequately reported inclusion and exclusion cri-
teria, and the timing of outcomes assessments (Schwenk et al., 2016;
Streckmann et al., 2014b; Wonders et al., 2013; Mizrahi et al., 2015;
Fernandes and Kumar, 2016). Three studies reported dropout ratio
(Schwenk et al., 2016; Wonders et al., 2013; Mizrahi et al., 2015), while
only Streckmann et al. (2014b) reported compliance ratio and applied
F. Duregon et al. Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx

the intention-to-treat analyses. Finally, one study performed follow-up

Results
evaluations (Mizrahi et al., 2015) and only Schwenk et al. (2016)

6/9
6/9
3/9
4/9
2/9
performed single blinding procedure (Tables 2 and 3).

Follow-up
3.2. CIPN symptoms

+
–
–
–

–
CIPN symptoms were investigated in four out of five studies with
Timing of outcomes assessment
different methods (Streckmann et al., 2014b; Wonders et al., 2013;
Mizrahi et al., 2015; Fernandes and Kumar, 2016). One study evaluated
symptoms only at baseline through a biothesiometer (Schwenk et al.,
2016), while the others evaluated symptoms pre- and post- exercise
training intervention. Specifically, Streckmann et al. (2014b) evaluated
peripheral deep sensitivity by a tuning fork with a graduating scale, and
found a significant decline in PNP symptoms (88%) in Intervention
Group (IG) compared with Control Group (CG) (0%). A decrease in PNP
+
+
+
+
+

symptoms was detected also in another study, which indicated a re-

Intention-to-treat analysis

duction of 98% in particular in the “Abnormally sensitive to touch”,

after 10 weeks of exercise training (Wonders et al., 2013). Similarly, the
Modified Total Neuropathy Score (mTNS) showed a statistically highly
significant decrease (−54%) at the end of the intervention (Fernandes
and Kumar, 2016); as a matter of fact, in this scale, ranged from 0 to 20,
a higher score represents worse neuropathy (Smith et al., 2010). In-
+
–
–
–
–

stead, in Mizrahi et al. (Mizrahi et al., 2015) there were no significant

Compliance

differences in the Functional Assessment Cancer Therapy-Neurotoxicity

(FACT-Neurotoxicity), a scale used to assess chemotherapy-induced
neurological symptoms (Huang et al., 2007).
+
–
–
–
–
Blinding

3.3. Static balance control

+
–

–
–
–

Four studies analyzed the influence of a specific exercise training

Dropouts

session on static balance control (Schwenk et al., 2016; Streckmann

et al., 2014b; Mizrahi et al., 2015; Fernandes and Kumar, 2016).
+
+
+
–

Streckmann et al. (2014b), who measured sway paths during static

Inclusion or exclusion criteria

monopedal stance through a force platform, showed an improvement in

the IG by 18% with a concurrent decline in the CG. Additionally, there
was also a significant intergroup difference for the failed attempts, with
the IG that achieved all tasks (100%) while the 40% of CG worsened
progressively. Both Streckmann et al. (2014b) and Schwenk et al.
(2016) did not find meaningful differences in the bipedal tasks with
eyes closed; conversely, there was an improvement in the bipedal tasks
with eyes opened, on feet closed (but not touching) and semi-tandem
+
+
+
+
+

positions (Schwenk et al., 2016). Indeed, Schwenk et al. (2016), using

Similarity of study groups

three wearable sensors, showed a reduction for the IG compared to the

CG in Medio-Lateral Center of Mass (COM) sway (55.5%), hip sway
(67.5%) and ankle sway (68.2%) during balance assessment with feet
closed, and in Medio-Lateral COM sway (47.6%), Antero-Posterior COM
sway (43.9%), and hip sway (74.8%) during evaluations in semi-
tandem position. A field test performance in Mizrahi and colleagues
demonstrated a significant increase by 64.5% after 12 weeks, and by
+
+
–
–
–

15% after 24 weeks in the single-leg balance test, within sample

Randomization procedure

(Mizrahi et al., 2015). Finally, it was assessed a significant improve-

ment (62%) in the Berg Balance Scale (BBS) after 15 sessions of seven
closed kinematic chain (CKC) exercises (Fernandes and Kumar, 2016).
Quality assessment of the included studies.

3.4. Dynamic balance control

+
+

The influence of exercise training session for cancer patients in

–
–
–

dynamic balance control was compared in two investigations (Schwenk

Fernandes and Kumar (2016)
Streckmann et al. (2014a,b)

et al., 2016; Streckmann et al., 2014b). The first used a foam pad, ad-
Schwenk et al. (2016)

justed on the top of the force platform, to evaluate the sway path on
Wonders et al. (2013)
Mizrahi et al. (2015)

monopedal (left/right) and bipedal stance (with open eyes)

(Streckmann et al., 2014b). After the acute bout of exercise, the IG
significantly reduced their sway paths by median 35.65% in the
Citation

monopedal tasks, while CG showed no changes (Streckmann et al.,

Table 1

2014b). Significant intergroup differences were also measured in

monopedal stance for failed attempts; thus, only 13% of the IG failed

4
 Table 2
Characteristics of the studies.
F. Duregon et al.

Author Subjects Age, y Groups, (n) Training modality, program and intensity Frequency Duration Compliance (C) and Dropout (n)
Adherence (A)

Streckmann et al. 56 (M 42/F 14) 44 IG IG (28) The IG trained with the supervision of a certified sport trainer (one-on- 1 h 2d/w 36 weeks C: 65% 2 (IG) 3 (CG)
(2014a,b) one). Aerobic endurance training: warm-up on a bicycle dynamometer
(60–70% HR max), 10–30 min on a treadmill or bicycle dynamometer
(70–80% HR max) at the end of the session;
[all of them undergoing 48 CG CG (28) Sensorimotor training: four postural stabilization tasks, progressively
chemotherapy] increasing tasks difficulty as well as surface instability (20 s exercise
+ 20 s rest for 3 sets, 1 min rest between different exercises);
Strength training: four different resistance exercises performed with
Thera-Band, at maximum force.
Schwenk et al. 22 (M 9/F 13) 68.73 ± 8.72 IG IG (11) During the exercises, the participants stood in front of the computer 45 min 4 weeks n.r. 2 (IG) 1 (CG)
(2016) [12 of them undergoing screen. A supervisor gave instructions during the first training session,
chemotherapy] then the participants conducted exercises using interactive sensor
feedback. The supervisor remained with the participants to guarantee
their safety.
71.82 ± 8.85 CG CG (11) The training sessions included: 1. Ankle point-to-point reaching tasks: 2 d/w
weight shifting in forward/backward direction and sideward/diagonal
direction, while standing in front of the computer screen, controlling
the movements of the ankle and body’s center of mass. Each session
included 6 blocks each with 20 cycles of ankle reaching.
2. Virtual obstacle crossing tasks: participants crossed virtual obstacles
moving on the computer screen from the left to the right side. Each
session included 3 series of obstacle crossing with 10 repetitions each,

5
with a progressive increase in obstacle height (10, 15, and 20% of leg
length).
Wonders et al. 14 F 51.6 ± 2.6 P (14) Each woman was given a home-based exercise program, along with 10 min 10 weeks n.r. 8 (IG)
(2013) [8 of them undergoing three exercise Thera-Band and a pedometer. The suggested goal was 2d/w (week 1)
chemotherapy] walking and doing resistance training exercises with specific frequency 30 min
and duration. Women were instructed to perform the home-based 5d/w (week 10) for
exercise program at moderate-intensity (55–65% of their estimated HR aerobic training;
max) and their goals were increased gradually over the 10 week period. 3d/w (all 10 weeks) for
resistance training.
Mizrahi et al. (2015) 30 F 58.6 ± 10.9 P (30) Participants were prescribed home-based, individualized, and low- 10 to 40 min 12 weeks n.r. 9 (IG)
moderate intensity exercise, for 90 min per week.
[all of them undergoing Aerobic exercise: walking, cycling or swimming (55–70% HR max); 3–4 d/w
chemotherapy] Strength training: resistance bands and body weight exercises (3 sets/
10 reps, 50–70% 1RM);
Core stability: floor and stability ball exercises (11–14 RPE).
Fernandes and 25 (M 12/F 13) 47 ± 12 P (25) The intervention was conducted at a tertiary care cancer hospital. 12 min for each exercise 3 weeks n.r. n.r.
Kumar (2016) Closed kinematic chain exercises were performed daily on a firm (for a total of 7 exercises)
surface, and were administered for a total of 15 sessions over 3 weeks.
[all of them undergoing Each exercise lasted for 12 min, and consisted of: 5 d/w
chemotherapy] 1. Open chain active ankle range of motion; 2. Bipedal toe raises and
heel raises; 3. Bipedal inversion and eversion; 4. Unipedal toe raises
and heel raises; 5. Unipedal inversion and eversion; 6. Wall slides; 7.
Unipedal balance for time, with eyes open.
Initially, patients started with one set of 5/10 repetitions, and increased
gradually to a total of three sets for each exercise.

F = female; M = male; IG = intervention group; CG = control group; P = population; HR max = heart rate maximum; 1RM = one repetition maximum; RPE = rate perceived exertion; reps = repetitions; min = min; n.r. = not reported.
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
 Table 3
Results.

Authors Group (n) CIPN Symptoms Static Balance Control Dynamic Balance Control Quality of Life and Physical Function
F. Duregon et al.

Streckmann IG (26) PNP Incidence [No. (%)] Balance control on a static surface Balance control on a dynamic surface EORTC-QLQ-C-30 [Mean/Median
et al. p = 0.398 T3-T0: 8 (30) (range)] p = 0.028** T1-T0: 9.1/8.3
(2014a,b) (-25 to 58)
PNP Decline [No. (%)] SMT sway [Median (range)] Static left p = 0.035** T3-T0: SMT sway [Median (range)] Dynamic left p = 0.113; p = 0.033* T3-T0: 12/16.6
p < 0.001** T3-T0: 7 (88) −17.75(-32 to 23) p = 0.007** T3-T0: −14.80(-134 to 6) Dynamic (-67 to 67)
right p = 0.045** T3-T0: −22.35(-167 to 5)
SMT failed attempts [No. (%)] Static left p = 0.024** T3: 01(4) SMT failed attempts [No. (%)] Dynamic left
Static right p = 0.075 T3: 02(8) p = 0.014** T3: 04(15) Dynamic right
p < 0.001** T3: 03(11)
Balance control following mechanical perturbation
PM sway [Median(range)] Med/lat bipedal
p = 0.006** T3-T0: −14.5(-42 to 9) Ant/post
bipedal p = 0.049** T3-T0: −21.2(-38 to 5)
Monopedal p = 0.009** T3-T0: −60.3(-81 to 26)
PM failed attempts [No. (%)] Monopedal
p = 0.002** T3: 1(4)
Time (t) [Median(range)] Med/lat bipedal
p = 0.045** T3-T0: −0.26(-11 to 25)Ant/post
bipedal p = 0.007** T3-T0: −0.26(-9 to 8)
CG (25) PNP Incidence [No. (%)] Balance control on a static surface Balance control on a dynamic surface EORTC-QLQ-C-30 [Mean/Median
p = 0.398 T3-T0: 12 (44) (range)] p = 0.028** T1-T0: −6.15/0
(-50 to 17)
PNP Decline [No. (%)] SMT sway [Median (range)] Static left p = 0.035** T3-T0: SMT sway [Median (range)] Dynamic left p = 0.113; p = 0.920 T3-T0: −1/0 (-66
p < 0.001** T3-T0 : 0 (0) 0.88(-108 to 31) p = 0.007** T3-T0: 0(-88 to 24) Dynamic right to 42)
p = 0.045** T3-T0: 0(-43 to 9)

6
SMT failed attempts [No. (%)] Static left p = 0.024** T3:
09(36) Static right p = 0.075 T3: 08(32)
SMT failed attempts [No. (%)] Dynamic left
p = 0.014** T3: 14(56) Dynamic right
p < 0.001** T3: 16(64)
Balance control following mechanical perturbation
PM sway [Median(range)] Med/lat bipedal
p = 0.006** T3-T0: 10.3(-13 to 13) Ant/post
bipedal p = 0.049** T3-T0: −9.8(-73 to 23)
Monopedal p = 0.009** T3-T0: 0(-61 to 69)
PM failed attempts [No. (%)] Monopedal
p = 0.002** T3: 11(44)
Time (t) [Median(range)] Med/lat bipedal
p = 0.045** T3-T0: 0.2(-3 to 13) Ant/post bipedal
p = 0.007** T3-T0: 0.27(-5 to 16)
(continued on next page)
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
 Table 3 (continued)

Authors Group (n) CIPN Symptoms Static Balance Control Dynamic Balance Control Quality of Life and Physical Function

Schwenk et al. IG (9) Feet closed − EO Gait Speed [m/s] p = 0.445 T0: 0.85 ± 0.27 T1: Fear of falling FES-I score p = 0.308 T0:
F. Duregon et al.

(2016) 0.92 ± 0.18 (+8.2%) 35.10 ± 13.18 T1: 32.60 ± 14.83

(-7.1%)
CoM sway − ML [cm] p = 0.022** T0: 2.72 ± 1.42 T1: Step time variability [CV] p = 0.734 T0:
1.21 ± 0.45 (-55.5%) 4.38 ± 2.81 T1: 3.42 ± 2.02 (-21.9%)
CoM sway − AP [cm] p = 0.251 T0: 1.61 ± 0.95 T1:
1.33 ± 0.86 (-17.4%)
Hip sway [deg2] p = 0.010** T0: 2.00 ± 1.91 T1:
0.65 ± 0.37 (-67.5%)
Ankle sway [deg2] p = 0.011** T0: 2.92 ± 4.01 T1:
0.93 ± 1.03 (-68.2%) Semi-tandem − EO
CoM sway − ML [cm] p = 0.035** T0: 3.15 ± 1.54 T1:
1.65 ± 0.65 (-47.6%)
CoM sway − AP [cm] p = 0.012** T0: 2.23 ± 1.06 T1:
1.25 ± 0.48 (-43.9%)
Hip sway [deg2] p = 0.008** T0: 3.22 ± 3.58 T1:
0.81 ± 0.67 (-74.8%)
Ankle sway [deg2] p = 0.294 T0: 3.77 ± 3.41 T1:
1.01 ± 0.91 (-73.2%)
Feet closed − EC
CoM sway − ML [cm] p = 0.304 T0: 3.78 ± 1.64 T1:
2.46 ± 1.36 (-34.9%)
CoM sway − AP [cm] p = 0.550 T0: 2.60 ± 1.15 T1:
2.39 ± 1.91 (-8.1%)
Hip sway [deg2] p = 0.305 T0: 4.22 ± 3.47 T1: 2.57 ± 2.24
(-39.1%)

7
Ankle sway [deg2] p = 0.277 T0: 5.96 ± 5.14 T1:
4.49 ± 6.65 (-24.7%)
CG (10) Feet closed − EO Gait Speed [m/s] p = 0.445 T0: 1.03 ± 0.17 T1: Fear of falling FES-I score p = 0.308 T0:
1.07 ± 0.20 (+3.9%) 28.20 ± 8.30 T1: 31.10 ± 9.46
(+10.3%)
CoM sway − ML [cm] p = 0.022** T0: 2.26 ± 1.27 T1: Step time variability [CV] p = 0.734 T0:
1.78 ± 0.91 (-21.2%) 3.64 ± 1.03 T1: 2.95 ± 1.97 (-19%)
CoM sway − AP [cm] p = 0.251 T0: 1.48 ± 1.00 T1:
1.53 ± 0.87 (+3.4%)
Hip sway [deg2] p = 0.010** T0: 2.34 ± 2.11 T1:
1.35 ± 0.97 (-42.3%)
Ankle sway [deg2] p = 0.011** T0: 2.10 ± 1.89 T1:
1.65 ± 1.25 (-21.4%)
Semi-tandem − EO
CoM sway − ML [cm] p = 0.035** T0: 2.13 ± 0.81 T1:
2.47 ± 1.37 (+16%)
CoM sway − AP [cm] p = 0.012** T0: 1.99 ± 1.57 T1:
1.94 ± 1.17 (-2.5%)
Hip sway [deg2] p = 0.008** T0: 1.94 ± 1.84 T1:
2.15 ± 1.71 (+10.8%)
Ankle sway [deg2] p = 0.294 T0: 1.84 ± 1.70 T1:
1.97 ± 1.43 (+7,1%)
Feet closed − EC
CoM sway − ML [cm] p = 0.304 T0: 2.34 ± 1.27 T1:
2.53 ± 1.14 (+8.1%)
CoM sway − AP [cm] p = 0.550 T0: 1.74 ± 1.13 T1:
1.99 ± 1.45 (+14.4%)
Hip sway [deg2] p = 0.305 T0: 2.68 ± 3.45 T1: 3.06 ± 2.82
(+14.2%)
Ankle sway [deg2] p = 0.277 T0: 2.42 ± 2.14 T1:
3.10 ± 2.99 (+28.1%)
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx

(continued on next page)

 Table 3 (continued)

Authors Group (n) CIPN Symptoms Static Balance Control Dynamic Balance Control Quality of Life and Physical Function
F. Duregon et al.

Wonders et al. P (6) LANSS-Q Unpleasant skin
(2013) sensations p = 0.05 Pre-HBE: 6
Post-HBE: 3 (-50%)
Abnormally sensitive to touch
p = 0.05* Pre-HBE: 6 Post-HBE: 1
(-83.3%)
Sudden bursts p = 0.05 Pre-HBE:
5 Post-HBE: 4 (-20%)
No Group Control
Mizrahi et al. P (post: 21; follow up: FACT-Ntx T0: 45.0 (5.9) T1: 44.3
(2015) 12) (7.2) p = 0.628 (-1.6%) T2: 45.4
(6.2) p = 0.830(+2.5%)
McGill QOL-Q p = 0.05* Pre-HBE:
7.25 +/− 0.3 Post-HBE: 3 +/− 0.4
(-58.6%)
Single-leg balance [s] T0: 30.4 (28.6) T1: 47.1 (28.6) 30-s sit to stand [No.] T0: 14.3 (4.5) T1:
p = 0.003* (+54.9%) T2: 40.1 (19.9) p ≤ 0.05* (-14.9%) 17.8 (4.7) p = 0.004* (+24.5%) T2:
19.0 (5.4) p = 0.100 (+6.7%)
Seated supported-row [kg] T0: 22.4
(5.0) T1: 25.8 (5.5) p = 0.001*
(+15.2%) T2: 27.1 (4.9) p = 0.002*
(+5%)
Supine leg press machine [kg] T0: 28.1
(7.5) T1: 35.9 (11.8) p = 0.003*
(+27.8%) T2: 45.0 (14.2) p = 0.001*
(+25.3%)
SF-36 physical function T0: 41.6 (9.8)
T1: 46.3 (6.1) p = 0.027* (+11.3%)
T2: 46.0 (6.7) p = 0.210 (-0.6%)
Global QOL T0: 101.3 (22.1) T1: 109.9
(21.0) p = 0.017* (+8.5%) T2: 116.6
(16.5) p = 0.004* (+6.1%)

8
No Group Control
Fernandes P (25) mTNS [score] p < 0.05* T0: BBS [score] p < 0.05* T0: 26 ± 2 T1: 42 ± 2(+62%)
and 13 ± 1 T1: 6 ± (-54%)0.9
Kumar
(2016)
No Group Control

* = Comparison-within group; ** = Comparison-between groups

No. = number; IG = intervention group; CG = control group; P = population; PNP = peripheral neuropathy; SMT = sensorimotor training; PM = mechanical perturbation; ML = medial/lateral; AP = anterior/posterior; EORTC-QOL-C30 = The
European Organisation for Research and Treatment of Cancer – Quality of Life – C30; EO = eyes opened; EC = eyes closed; CoM = center of mass; FES-I = Falls Efficacy Scale-International; LANSS-Q = Leeds Assessment of Neuropathic Symptoms
and Signs – Questionnaire; HBE = home-based exercise; McGill QOL-Q = McGill Quality of Life Questionnaire – level of troublesome symptoms from 1 to 10; FACT-Ntx = the Functional Assessment Cancer Therapy-Neurotoxicity; SF-36 physical
function = Medical Outcome Study 36-item Short Form; mTNS = Modified Total Neuropathy Score; BBS = Berg Balance Scale.
Pre-post variations, where possible, has been reported in percentage of change.
Original data appeared as follow.
Streckmann et al. (2014a,b): CIPN Symptoms, SMT failed attempts, PM failed attempts [No. (%)]; SMT sway, PM sway, Time [Median(range)]; EORTC-QLQ-C30 [Mean/Median(range)].
Schwenk et al. (2016), Mizrahi et al. (2015), Fernandes and Kumar (2016): all data [Mean(SD)].
Wonders et al. (2013): LANSS-Q [No.]; McGill QOL [Mean(SE)].
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
F. Duregon et al.
attempts compared to the CG (60%) (Streckmann et al., 2014b).
Balance control was verified through an oscillating 2D platform,
which followed a mechanical perturbation impulse. In bipedal tasks the
IG significantly reduced sway paths (average 30%), both in antero-
posterior and medio-lateral oscillations, as well as in monopedal task
(52.6%), in comparison with CG (Streckmann et al., 2014b). The IG
accomplished all perturbation tasks (100%) on the contrary CG pro-
gressively declined the performance with a 60% failed attempts
(Streckmann et al., 2014b). Finally, the IG significantly improved time
necessary to regain balance after a perturbation by 0.32 s (Streckmann
et al., 2014b), while for the CG the time for repositioning appeared as
unchanged. The second study investigated dynamic balance control
with gait performance, using wearable sensors; for this investigation, no
significant changes were noted in both IG and CG (Schwenk et al.,
2016).
3.5. Quality of life and physical function
Different questionnaires and scales were proposed to assess the QOL
(EORTC-QLQ-C-30, SF-36, FACT-O), fear of falling (FES-I), and level of
troublesome symptoms (McGill QOL Questionnaire). Significant dif-
ferences in QOL were found after 12 weeks of exercise intervention
training, in both the between groups comparison (Streckmann et al.,
2014b), and in the within condition (11.3%) (Mizrahi et al., 2015).
Mizrahi et al. (2015) also evaluated QOL in the domains of “physical”,
“social”, “emotional”, “function”, and “ovarian cancer-specific well-
being”; they found significant intragroup improvements in the global
QOL after 12 weeks of exercise intervention (8.4%) and after 24 weeks,
during the follow-up session (6.1%). Similarly, in Streckmann et al.
(2014b), IG significantly improved their QOL after 36 weeks of inter-
vention. Moreover, while Schwenk et al. (2016) did not found sig-
nificant changes in fear of falling after 4 weeks of exercise training,
Wonders et al. (2013) assessed a reduction (-58.62%) in the ques-
tionnaire about levels of troublesome CIPN symptoms, after 10 weeks of
home-based exercise.
Only one study evaluated physical function with three different field
tests, to measure respectively upper and lower body strength and lower
body functional capacity (Mizrahi et al., 2015). Significant improve-
ments were displayed from baseline to 12 weeks of exercise training,
and also from baseline to 24-week follow up in upper (15.17%; 21%)
and lower body strength (27.8%; 60.14%) (Mizrahi et al., 2015). There
was also an improvement in lower body functional capacity (24.5%)
from baseline to 12 weeks of exercise training; no significant changes
were found at follow up (Mizrahi et al., 2015).
4. Discussion
This literature review aimed to summarize and analyze the existing
evidence of the effects secondary to exercise interventions in patients
showing PNP induced by chemotherapy. Firstly, at the light of the re-
ported results, specific exercise protocols have been demonstrated as
feasible for cancer patients undergoing chemotherapy. Indeed, 122
subjects positively concluded their interventions, despite the concrete
difficulty due to the parallel therapeutic treatment concurring to de-
termine weakness and fatigue. Physical exercise has been also showed
useful to contrast the CIPN symptoms, improving QOL and Activities of
Daily Living (ADLs). Basically, consistent improvements were found on
the static balance control and QOL. Overall, other meaningful changes
on dynamic balance control, physical function, further, a lower in-
cidence of CIPN symptoms were found. It has to be mentioned that
results would seem to be attributable to the different exercise protocols.
Moreover, all studies did not evaluate all parameters and there was a
large heterogeneity among investigations, such as workout types and
durations were almost different. Additionally, methods of assessment
were not comparable in all investigations; for example, balance control
was measured with different techniques (Schwenk et al., 2016;
9
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
Streckmann et al., 2014b; Mizrahi et al., 2015; Fernandes and Kumar,
2016); similarly, QOL was quantified by different questionnaires
(Schwenk et al., 2016; Streckmann et al., 2014b; Wonders et al., 2013;
Mizrahi et al., 2015).
4.1. CIPN symptoms
Four out of five studies investigated levels of CIPN symptoms in
cancer patients using different methods; in three of them there was a
significant decline of reported symptoms (Streckmann et al., 2014b;
Wonders et al., 2013; Fernandes and Kumar, 2016). In particular, the
longer intervention training which lasted 36 weeks, produced notable
results (Streckmann et al., 2014b). This study proposed a mixed
workout with aerobic, strength and sensorimotor training; among these,
a specific focus on stabilization tasks was required, with an increasing
difficulty such as the surface instability (Streckmann et al., 2014b). A
shorter exercise intervention also focused specifically on balance con-
trol, and gaining remarkable improvements (Fernandes and Kumar,
2016). On the contrary, in the selected study of Wonders and Collea-
gues (Wonders et al., 2013) there were significant ameliorations only in
the “Abnormally sensitive to touch” subscale. However, it has to be
underlined that the home-based exercise program lasted 10 weeks, with
a suggested target identified in walking task and performing resistance
training, without introducing specific proprioception exercises. At the
light of the reported results, we could suppose some considerations
about the physical exercise in the presence of CIPN symptoms. Firstly,
the specificity of intervention, such as a sensorimotor training, could
play an important role in reducing CIPN manifestations, for example
risk of fall. As a matter of fact, in a recent study the incidence of falls in
community-dwelling older people reduced after a one-year static bal-
ance and proprioception program (Perez-Ros et al., 2016). Secondly, a
longer period of training could contribute to obtain more notable re-
sults. This suggestion was also underlined in a 4-year prospective ran-
domized intervention study, in type II diabetes patients (Balducci et al.,
2006). The prolonged exercise, focused on the gait dynamics with a
brisk walking on a treadmill, showed clinical meaningful improvements
modifying the development of motor diabetic neuropathy (Balducci
et al., 2006). It may be interestingly to analyze if a specified exercise
intervention in cancer patients, administered from the beginning of
therapy and prolonged after, could modify the natural history of CIPN.
4.2. Static balance control
Static balance control was investigated by four out of five studies,
and clinical meaningful improvements were found in all of them
(Schwenk et al., 2016; Streckmann et al., 2014b; Mizrahi et al., 2015;
Fernandes and Kumar, 2016). Although reports described different as-
sessments and protocols, interventions included in each session a sen-
sorimotor training and postural exercises, such as stabilization tasks
(Streckmann et al., 2014b), closed kinematic chain exercises, core sta-
bility and balance training (Schwenk et al., 2016; Mizrahi et al., 2015;
Fernandes and Kumar, 2016). Among these, the single-leg balance test
ameliorated after 12 weeks of exercise training and improvements were
also maintained after 24 weeks, doing the follow up assessment
(Mizrahi et al., 2015). Thus, it appears that sensorimotor training has
the potential to influence neuromuscular mechanisms in order to im-
prove balance performance, as suggested in another investigation. In-
deed, Song and Colleagues (Song et al., 2011), involving diabetic pa-
tients, showed that balance control and trunk proprioception improved
after balance exercises advocating that this specific intervention can be
suitable for individuals with DPN. Moreover, Schwenk et al. (2016)
proposed a novel approach to workout, including repetitive weight
shifting and virtual obstacle crossing tasks, which led to great im-
provements (ranged from 43% to 74%). The interactive game-based
balance training, with a visual computer-feedback, was also used in
other clinical conditions, such as diabetes (Grewal et al., 2015),
F. Duregon et al.
multiple sclerosis (Prosperini et al., 2010), post-stroke (Srivastava et al.,
2009). Thus, this innovative method revealed feasible in various dis-
eases, all characterized by balance impairments, contributing to the
introduction of new technologies in physical exercise training.
Interestingly, in two studies (Schwenk et al., 2016; Streckmann
et al., 2014b), it has been reported significant positive changes after the
exercise protocol only in the open-eye condition although both in-
vestigations included blinded (with visual deprivation) tasks in their
original protocols. It can be speculated that patients paid more atten-
tion on the visual feedback during the intervention rather than pro-
prioception. In particular in Schwenk et al. (2016) visual feedback was
given during the tasks in order to provide more detailed information
about lower-extremity motion. Thus, results may be explained by the
visual influence on balance, measured with eyes open, in comparison
with the closed eyes condition (Schwenk et al., 2016). In future, it may
be useful to explore the potential usefulness of other feedbacks (e.g.
auditory or tactile) to stimulate balance with eyes closed and dual-
tasking conditions (cognitive- plus motor-task) (Zanotto et al., 2014;
Bergamin et al., 2014).
4.3. Dynamic balance control
Two studies assessed dynamic balance control (Schwenk et al.,
2016; Streckmann et al., 2014b), and only one of them showed sig-
nificant improvements (Streckmann et al., 2014b). Specifically, in
balance control on dynamic surface, improvements were found in
monopedal stance, presumably due to the continuous weight shifting
during the virtual obstacle-crossing task (Streckmann et al., 2014b).
Instead, in bipedal stance with open eyes there were no improvements
and it can be supposed that, in dynamic balance control, it is not suf-
ficient visual feedback but there could be other influential factors.
Particularly, an exercise training focused on dynamic control should
also pay attention on gait performance. As Mustapa et al. (Mustapa
et al., 2016) showed in a recent review, gait in diabetic patients with
peripheral neuropathy is known as conservative, and occurs with high
double support time, slow speed, and shorter steps as an attempt to
keep stability in walking. Thus, it could be efficient to introduce
walking tasks (for example, tandem walk or other different kinds of
stride), and functional exercises (for example, sitting to standing on a
chair, walking up and down a slope, stair climbing and mini hops),
increasing gradually the complexity of the workout, as Allet and Col-
leagues (Allet et al., 2010) already tested with a group of diabetic pa-
tients.
Regarding balance control following mechanical perturbation, the
IG showed great improvements in all tasks, both monopedal and bi-
pedal, on the contrary CG were unable to maintain balance and failed
attempts more times (Streckmann et al., 2014b). Probably these posi-
tive changes are associated with sensorimotor training introduced in
each session, and they cannot be achieved with endurance or strength
training alone. In line with these findings, previous studies in healthy
adults have revealed that sensorimotor training can improve balance
control and diminish the prevalence of falls (Taube et al., 2008).
4.4. Quality of life and physical function
Literature has already demonstrated the important role of physical
exercise on quality of life (Gillison et al., 2009) in healthy population,
not only by increasing performance on activities of daily living (Hanson
and Jones, 2015), but also by improving mental health (Bize et al.,
2007). Similarly, in patients with heterogeneous causes of neuropathy,
participation in the exercise protocol may be determinant to improve
the physical and the mental functions together with the health related
quality of life (Graham et al., 2007). On this matter, included articles
reported meaningful changes in quality of life of cancer patients into IG
(Streckmann et al., 2014b; Wonders et al., 2013; Mizrahi et al., 2015);
only in Schwenk et al. (2016) the participants’ fear of falling did not
10
Critical Reviews in Oncology / Hematology xxx (xxxx) xxx–xxx
change significantly, probably because the 4-week intervention period
may have been too short to significantly change this parameter. Instead,
in the other studies, interventions lasted more weeks (from 10 to 36
weeks) and the benefits on quality of life also remained until the follow
up period (Mizrahi et al., 2015). Hence, it can be supposed that im-
provements in QOL could be, in some way, influenced by the duration
of the interventions, even basing on a combination of aerobic, strength,
and sensorimotor training. Actually, it was showed that also a 12-week
yoga program improved various domains of QOL in early-stage breast
cancer patients (Galantino et al., 2012), that practiced the protocol
throughout the therapies. In fact, patients reported positive responses
about the breathing techniques and the stretching, that helped them
during adverse events of chemotherapy. Thus, we suppose that a mixed
physical exercise combined with alternative activities, such as yoga,
could considerably ameliorate some aspects of QOL of cancer patients
ongoing chemotherapy.
Unlike QOL, the results on physical function was evaluated only by
Mizrahi et al. (2015) that found significant changes. In particular, they
showed notable improvements both on upper and lower body strength,
and on lower body functional capacity. On this matter, participants
maintained their physical exercise levels at the follow up, suggesting
that a lifestyle change had been successfully adopted (Mizrahi et al.,
2015). Therefore, it may be supposed that exercise training strongly
contributes to the QOL and physical function, as demonstrated for
ovarian cancer patients (Mizrahi et al., 2015); as well as, exercise could
prevent the unavoidable consequences of physical inactivity during
chemotherapy, that include muscle atrophy, osteopenia, declines in
cardiorespiratory fitness, decreased insulin sensitivity, decreased im-
mune function, and increased risk of chronic illness (JAMA, 1996).
4.5. Limitations
Several limitations have to be considered in interpreting the results
of this summary of the literature. First, although the large number of
records identified through database searching, studies included in
qualitative synthesis, corresponding on the inclusion criteria, were very
few. Thus, there was a small sample size that was furthermore non-
homogeneous both in age, and in therapy, because participants re-
ceived first, second, third-line or higher chemotherapy treatment. The
various timings of treatment could have influence the incidence of the
CIPN, and the different average that have impacted on balance control.
Particularly the older patients may be less able to compensate for the
loss of proprioception compared to younger patients (Schwenk et al.,
2016). There was a large heterogeneity also in the measured outcomes
that did not permit an unbiased meta-analytic approach. Moreover,
only the Streckmann et al. study (Streckmann et al., 2014b) precisely
quantified the real frequency of the exercise sessions, thus it was not
possible to obtain a relation (or correlation) between the adherence (in
term of frequency) and the potential acquirable benefits. With the same
principle of reasoning, not all the studies specified how much lines of
chemotherapy treatment were administered and the real basal condi-
tion when participants began the interventions (only inclusion criteria
were specified). Therefore, it is difficult to precisely indicate when
ideally starting the physical exercise, if as soon as possible with the
treatment beginning or only in case of neurological defect. Ad-
ditionally, quality appraisal classified three out of five studies as low
quality (Wonders et al., 2013; Mizrahi et al., 2015; Fernandes and
Kumar, 2016); there may be possible biases about the results. For ex-
ample, the positive results described in the three investigations without
control group (Wonders et al., 2013; Mizrahi et al., 2015; Fernandes
and Kumar, 2016), could not ascribable to the exercise protocols. Fi-
nally, another point to be considered is that manuscripts described
different interventions; although they had a similar structure (en-
durance, strength, balance and sensorimotor training) there were dif-
ferent intensities, durations, and modalities.
F. Duregon et al.
5. Conclusions
Results from this systematic review showed that different exercise
protocols for cancer patients, undergoing treatment with CIPN symp-
toms are feasible and effective. Significant improvements were found
on postural control with a parallel counteraction on the common
symptoms of CIPN. Furthermore, quality of life for cancer patients
ameliorated after the exercise training. In particular, positive effects
were associated with a combined exercise protocol including en-
durance, strength and sensorimotor training. At the light of the reported
outcomes, a starting point for a broad-spectrum exercise indication
designed for these cancer patients undergoing chemotherapy should
include aerobic exercise, total body strength training and propriocep-
tive training, ideally with duration not inferior than 36 weeks.
Moderate intensities for aerobic and strength trainings should be sug-
gested with a frequency within 2–5 days per week; maximal session
duration should be no longer than 60 min for each exercise session.
However, it is also important to affirm that further investigations are
strongly needed to reinforce the current small source of data defining
future standards for exercise prescription.
Conflicts of interest
None.
Acknowledgements
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
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