Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe and common side effect caused by a variety of antineoplastic agents. Approximately 30–40% of patients treated with agents such as taxanes, vinca alkaloids, or platinum derivatives will develop CIPN. CIPN presents predominantly as a sensory axonal neuro(no)pathy with occasional motor and autonomic dysfunction exhibiting considerable variability of clinical symptoms ranging from mild tingling sensation to severe neuropathic pain. Typical symptoms include numbness (“minus symptom”), weakness, and abnormal gait as well as paresthesia and pain (“positive symptoms”). As CIPN symptoms potentially lead to long-term morbidity and can even aggravate after cessation of therapy, patients’ quality of life can be tremendously affected. In view of improved breast cancer survival outcomes, the late effects of CIPN are an unmet need in these patients. Therefore, early detection and assessment of first symptoms is important to effectively prevent severe CIPN. Therapeutic options for patients with CIPN are still limited, and pharmacological treatment focuses primarily on reduction or relief of neuropathic pain. CIPN is usually acutely managed by dose reduction or discontinuation of causative chemotherapy, potentially compromising treatment outcome. Currently, there is no causative proven therapy for the prevention of CIPN.

1.
Park
SB
,
Goldstein
D
,
Krishnan
AV
,
Lin
CS
,
Friedlander
ML
,
Cassidy
J
, et al.
Chemotherapy-induced peripheral neurotoxicity: a critical analysis
.
CA Cancer J Clin
.
2013
Nov-Dec
;
63
(
6
):
419
37
.
[PubMed]
0007-9235
2.
Kandula
T
,
Farrar
MA
,
Kiernan
MC
,
Krishnan
AV
,
Goldstein
D
,
Horvath
L
, et al.
Neurophysiological and clinical outcomes in chemotherapy-induced neuropathy in cancer
.
Clin Neurophysiol
.
2017
Jul
;
128
(
7
):
1166
75
.
[PubMed]
1388-2457
3.
Winters-Stone
KM
,
Horak
F
,
Jacobs
PG
,
Trubowitz
P
,
Dieckmann
NF
,
Stoyles
S
, et al.
Falls, Functioning, and Disability Among Women With Persistent Symptoms of Chemotherapy-Induced Peripheral Neuropathy
.
J Clin Oncol
.
2017
Aug
;
35
(
23
):
2604
12
.
[PubMed]
0732-183X
4.
Hershman
DL
,
Weimer
LH
,
Wang
A
,
Kranwinkel
G
,
Brafman
L
,
Fuentes
D
, et al.
Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy
.
Breast Cancer Res Treat
.
2011
Feb
;
125
(
3
):
767
74
.
[PubMed]
0167-6806
5.
Hershman
DL
,
Till
C
,
Wright
JD
,
Awad
D
,
Ramsey
SD
,
Barlow
WE
, et al.;
Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials
.
Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials
.
J Clin Oncol
.
2016
Sep
;
34
(
25
):
3014
22
.
[PubMed]
0732-183X
6.
Jordan
K
,
Feyer
P
,
Höller
U
,
Link
H
,
Wörmann
B
,
Jahn
F
.
Supportive Treatments for Patients with Cancer
.
Dtsch Arztebl Int
.
2017
Jul
;
114
(
27-28
):
481
7
.
[PubMed]
1866-0452
7.
Argyriou
AA
,
Bruna
J
,
Genazzani
AA
,
Cavaletti
G
.
Chemotherapy-induced peripheral neurotoxicity: management informed by pharmacogenetics
.
Nat Rev Neurol
.
2017
Aug
;
13
(
8
):
492
504
.
[PubMed]
1759-4758
8.
Staff
NP
,
Grisold
A
,
Grisold
W
,
Windebank
AJ
.
Chemotherapy-induced peripheral neuropathy: A current review
.
Ann Neurol
.
2017
Jun
;
81
(
6
):
772
81
.
[PubMed]
0364-5134
9.
Paice
JA
.
Clinical challenges: chemotherapy-induced peripheral neuropathy
.
Semin Oncol Nurs
.
2009
May
;
25
(
2
Suppl 1
):
S8
19
.
[PubMed]
0749-2081
10.
Jordan
K
,
Aapro
M
,
Kaasa
S
,
Ripamonti
CI
,
Scotté
F
,
Strasser
F
, et al.
European Society for Medical Oncology (ESMO) position paper on supportive and palliative care
.
Ann Oncol
.
2018
Jan
;
29
(
1
):
36
43
.
[PubMed]
0923-7534
11.
Cella
D
,
Peterman
A
,
Hudgens
S
,
Webster
K
,
Socinski
MA
.
Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane)
.
Cancer
.
2003
Aug
;
98
(
4
):
822
31
.
[PubMed]
0008-543X
12.
Hershman
DL
,
Lacchetti
C
,
Dworkin
RH
,
Lavoie Smith
EM
,
Bleeker
J
,
Cavaletti
G
, et al.;
American Society of Clinical Oncology
.
Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: american Society of Clinical Oncology clinical practice guideline
.
J Clin Oncol
.
2014
Jun
;
32
(
18
):
1941
67
.
[PubMed]
0732-183X
13.
Guo
Y
,
Jones
D
,
Palmer
JL
,
Forman
A
,
Dakhil
SR
,
Velasco
MR
, et al.
Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial
.
Support Care Cancer
.
2014
May
;
22
(
5
):
1223
31
.
[PubMed]
0941-4355
14.
von Delius
S
,
Eckel
F
,
Wagenpfeil
S
,
Mayr
M
,
Stock
K
,
Kullmann
F
, et al.
Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study
.
Invest New Drugs
.
2007
Apr
;
25
(
2
):
173
80
.
[PubMed]
0167-6997
15.
Gandara
DR
,
Nahhas
WA
,
Adelson
MD
,
Lichtman
SM
,
Podczaski
ES
,
Yanovich
S
, et al.
Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities
.
J Clin Oncol
.
1995
Feb
;
13
(
2
):
490
6
.
[PubMed]
0732-183X
16.
Leal
AD
,
Qin
R
,
Atherton
PJ
,
Haluska
P
,
Behrens
RJ
,
Tiber
CH
, et al.;
Alliance for Clinical Trials in Oncology
.
North Central Cancer Treatment Group/Alliance trial N08CA-the use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled study
.
Cancer
.
2014
Jun
;
120
(
12
):
1890
7
.
[PubMed]
0008-543X
17.
Schloss
JM
,
Colosimo
M
,
Airey
C
,
Masci
P
,
Linnane
AW
,
Vitetta
L
.
A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN)
.
Support Care Cancer
.
2017
Jan
;
25
(
1
):
195
204
.
[PubMed]
0941-4355
18.
Hershman
DL
,
Unger
JM
,
Crew
KD
,
Till
C
,
Greenlee
H
,
Minasian
LM
, et al.;
Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine
.
SWOG S0715
.
J Natl Cancer Inst
.
2018
Jun
;
110
(
6
):
669
76
.
[PubMed]
0027-8874
19.
Albers
JW
,
Chaudhry
V
,
Cavaletti
G
,
Donehower
RC
.
Interventions for preventing neuropathy caused by cisplatin and related compounds
.
Cochrane Database Syst Rev
.
2014
Mar
;(
3
):
CD005228
.
[PubMed]
1469-493X
20.
Kautio
AL
,
Haanpää
M
,
Leminen
A
,
Kalso
E
,
Kautiainen
H
,
Saarto
T
.
Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms
.
Anticancer Res
.
2009
Jul
;
29
(
7
):
2601
6
.
[PubMed]
1791-7530
21.
Jordan
B
,
Jahn
F
,
Beckmann
J
,
Unverzagt
S
,
Müller-Tidow
C
,
Jordan
K
.
Calcium and Magnesium Infusions for the Prevention of Oxaliplatin-Induced Peripheral Neurotoxicity: A Systematic Review
.
Oncology
.
2016
;
90
(
6
):
299
306
.
[PubMed]
0030-2414
22.
Kuriyama
A
,
Endo
K
.
Goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis
.
Support Care Cancer
.
2018
Apr
;
26
(
4
):
1051
9
.
[PubMed]
0941-4355
23.
Pachman
DR
,
Dockter
T
,
Zekan
PJ
,
Fruth
B
,
Ruddy
KJ
,
Ta
LE
, et al.
A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I
.
Support Care Cancer
.
2017
Nov
;
25
(
11
):
3407
16
.
[PubMed]
0941-4355
24.
Ghoreishi
Z
,
Esfahani
A
,
Djazayeri
A
,
Djalali
M
,
Golestan
B
,
Ayromlou
H
, et al.
Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial
.
BMC Cancer
.
2012
Aug
;
12
(
1
):
355
.
[PubMed]
1471-2407
25.
Lai
XB
,
Ching
SS
,
Wong
FK
,
Leung
CW
,
Lee
LH
,
Wong
JS
, et al.
A Nurse-Led Care Program for Breast Cancer Patients in a Chemotherapy Day Center: A Randomized Controlled Trial
.
Cancer Nurs
.
2019
Jan/Feb
;
42
(
1
):
20
34
.
[PubMed]
1538-9804
26.
Sundar
R
,
Bandla
A
,
Tan
SS
,
Liao
LD
,
Kumarakulasinghe
NB
,
Jeyasekharan
AD
, et al.
Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study
.
Front Oncol
.
2017
Jan
;
6
:
274
.
[PubMed]
2234-943X
27.
Hanai
A
,
Ishiguro
H
,
Sozu
T
,
Tsuda
M
,
Yano
I
,
Nakagawa
T
, et al.
Effects of Cryotherapy on Objective and Subjective Symptoms of Paclitaxel-Induced Neuropathy: Prospective Self-Controlled Trial
.
J Natl Cancer Inst
.
2018
Feb
;
110
(
2
):
141
8
.
[PubMed]
0027-8874
28.
Tsuyuki
S
,
Senda
N
,
Kanng
Y
,
Yamaguchi
A
,
Yoshibayashi
H
,
Kikawa
Y
, et al.
Evaluation of the effect of compression therapy using surgical gloves on nanoparticle albumin-bound paclitaxel-induced peripheral neuropathy: a phase II multicenter study by the Kamigata Breast Cancer Study Group
.
Breast Cancer Res Treat
.
2016
Nov
;
160
(
1
):
61
7
.
[PubMed]
0167-6806
29.
Bao
T
,
Seidman
AD
,
Piulson
L
,
Vertosick
E
,
Chen
X
,
Vickers
AJ
, et al.
A phase IIA trial of acupuncture to reduce chemotherapy-induced peripheral neuropathy severity during neoadjuvant or adjuvant weekly paclitaxel chemotherapy in breast cancer patients
.
Eur J Cancer
.
2018
Sep
;
101
:
12
9
.
[PubMed]
0959-8049
30.
Jeong
YJ
,
Kwak
MA
,
Seo
JC
,
Park
SH
,
Bong
JG
,
Shin
IH
, et al.
Acupuncture for the Treatment of Taxane-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Trial
.
Evid Based Complement Alternat Med
.
2018
Oct
;
2018
:
5367014
.
[PubMed]
1741-427X
31.
Knoerl
R
,
Smith
EM
,
Barton
DL
,
Williams
DA
,
Holden
JE
,
Krauss
JC
, et al.
Self-Guided Online Cognitive Behavioral Strategies for Chemotherapy-Induced Peripheral Neuropathy: A Multicenter, Pilot, Randomized, Wait-List Controlled Trial
.
J Pain
.
2018
Apr
;
19
(
4
):
382
94
.
[PubMed]
1526-5900
32.
Kleckner
IR
,
Kamen
C
,
Gewandter
JS
,
Mohile
NA
,
Heckler
CE
,
Culakova
E
, et al.
Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial
.
Support Care Cancer
.
2018
Apr
;
26
(
4
):
1019
28
.
[PubMed]
0941-4355
33.
Schönsteiner
SS
,
Bauder Mißbach
H
,
Benner
A
,
Mack
S
,
Hamel
T
,
Orth
M
, et al.
A randomized exploratory phase 2 study in patients with chemotherapy-related peripheral neuropathy evaluating whole-body vibration training as adjunct to an integrated program including massage, passive mobilization and physical exercises
.
Exp Hematol Oncol
.
2017
Feb
;
6
(
1
):
5
.
[PubMed]
2162-3619
34.
Smith
EM
,
Pang
H
,
Cirrincione
C
,
Fleishman
S
,
Paskett
ED
,
Ahles
T
, et al.;
Alliance for Clinical Trials in Oncology
.
Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial
.
JAMA
.
2013
Apr
;
309
(
13
):
1359
67
.
[PubMed]
0098-7484
35.
Mishra
S
,
Bhatnagar
S
,
Goyal
GN
,
Rana
SP
,
Upadhya
SP
.
A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study
.
Am J Hosp Palliat Care
.
2012
May
;
29
(
3
):
177
82
.
[PubMed]
1049-9091
36.
Rao
RD
,
Flynn
PJ
,
Sloan
JA
,
Wong
GY
,
Novotny
P
,
Johnson
DB
, et al.
Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3
.
Cancer
.
2008
Jun
;
112
(
12
):
2802
8
.
[PubMed]
0008-543X
37.
Finnerup
NB
,
Attal
N
,
Haroutounian
S
,
McNicol
E
,
Baron
R
,
Dworkin
RH
, et al.
Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis
.
Lancet Neurol
.
2015
Feb
;
14
(
2
):
162
73
.
[PubMed]
1474-4422
38.
Cavaletti
G
,
Marmiroli
P
.
Pharmacotherapy options for managing chemotherapy-induced peripheral neurotoxicity
.
Expert Opin Pharmacother
.
2018
Feb
;
19
(
2
):
113
21
.
[PubMed]
1465-6566
39.
Fallon
MT
,
Storey
DJ
,
Krishan
A
,
Weir
CJ
,
Mitchell
R
,
Fleetwood-Walker
SM
, et al.
Cancer treatment-related neuropathic pain: proof of concept study with menthol—a TRPM8 agonist
.
Support Care Cancer
.
2015
Sep
;
23
(
9
):
2769
77
.
[PubMed]
0941-4355
40.
Simpson
DM
,
Robinson-Papp
J
,
Van
J
,
Stoker
M
,
Jacobs
H
,
Snijder
RJ
, et al.
Capsaicin 8% Patch in Painful Diabetic Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Study
.
J Pain
.
2017
Jan
;
18
(
1
):
42
53
.
[PubMed]
1526-5900
41.
Gewandter
JS
,
Mohile
SG
,
Heckler
CE
,
Ryan
JL
,
Kirshner
JJ
,
Flynn
PJ
, et al.
A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors
.
Support Care Cancer
.
2014
Jul
;
22
(
7
):
1807
14
.
[PubMed]
0941-4355
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