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. 2023 Jan 30;11(1):15. doi: 10.3390/medsci11010015

Table 1.

Summary of studies and results of consensus process regarding the options (O) for prevention (p) or/and treatment (t) of CIPN.

O for p or t Author 1 Study Design 2 p 3 t 3 Intervention Outcome Measures Result/Clinical Experience (CE) 4
Phytotherapy Arslan et al. 2020 [17] RCT (n = 60) √ - Henna application CIPN assessment tool Significant beneficial effect. Low cost, safe intervention, and well tolerated by patients.
Fallon et al. 2015 in S3 clinical guideline
Supportive therapy [37]		 Proof of concept study - √ Application of menthol crème 1% Brief Pain Inventory (BPI), Quantitative Sensory Testing Significant reduction in pain symptoms.
Izgu et al. 2019 [101] Pilot RCT (n = 46) - √ Aroma hand and foot massage. Neuropathic symptoms, numeric rating scale Significant lower severity of pain based on NRS.
Li et al. 2019 [35] Meta-analysis √ √ All types of Chinese herbal medicine in TCM CIPN grade, Levi’s grade Improvement of sensory nerve conduction velocity and motor nerve conduction velocity.
Noh et al. 2018 [36] Syst. Review of RCTs (n = 28) √ √ All types of Phy used for medicinal purposes Clinical improvement, nerve conduction study (NCS) Potentially preventive and/or therapeutic effects for CIPN
Noh and Park 2019 [50] RCT (n = 31) - √ Aroma foot reflexology CIPN assessment tool Statistically significant reduction of symptoms.
Rostami et al. 2019 [75] RCT (n = 34) - √ Topical c. colocynthis oil Functional Assessment of Cancer Therapy (FACT), Neurotoxicity score Failed to improve the symptoms of CIPN compared with placebo.
Consensus process N/A √ √ Aconit oil application Clinical improvement CE 3
Consensus process N/A √ Solum oil application Clinical improvement CE 1
Consensus process N/A √ √ Flaxseed bath Clinical improvement CE 4
Consensus process N/A √ √ Arnica comp/Formica oil application Clinical improvement CE 3
Consensus process N/A - √ Arnica comp/Formica ointment (for stronger effect of Aconit) Clinical improvement CE 3–4
Consensus process N/A - √ Rosemary ointment Clinical improvement CE 3–4
Consensus process N/A - √ Peppermint oil application for heat sensations and paraesthesia Clinical improvement CE2
Consensus process N/A - √ Eucalyptus oil application for heat sensations and paraesthesia Clinical improvement CE 2
Movement therapies Andersen et al. 2020 [38] Single-blind ex-ploratory RCT (n = 48) √ √ Physical therapy Patient questionnaires, quantitative sensory testing Improvement of CIPN pain for patients with breast cancer. Correlation to preservation of sensory function.
Brami et al. 2016 [16] Systematic review of RCTs (n = 13) - √ Physical activity Nerve conduction velocity, (NCV), Neurological Symptom Score, Total Neuropathy Score, QoL Evidence was reported for interventions consisting of physical activity components; for strength and endurance training; and for multimodal self-help strategies including physical activity, yoga, and mindfulness.
Fernandes and Kumar 2016 [69] Single-group pre-post prospective study (n = 25) - √ Closed kinematic chain exercise Modified Total Neuropathy Score (mTNS), Berg Balance Score (BBS) Significant change in values before and after the exercise.
Kanzawa-Lee et al. 2020 [54] Comprehensive inte-grative review(7 RCTs, 6 quasi-experimental studies) - √ Exercise with Aerobic, strength training, and balance training CIPN, balance, and fitness Empirical evidence is insufficient to definitively conclude that exercise interventions ameliorate CIPN.
Kleckner et al. 2018 [48] Secondary analysis of a phase III RCT (n = 355) - √ EXCAP©® a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program Patient-reported CIPN symptoms Reduction of CIPN symptoms (hot/coldness in hands/feet, numbness, and tingling).
McCrary et al. 2019 [84] Prospective pilot intervention study, single group pre-post design (n = 35) - √ 8-week multimodal exercises (resistance, balance, cardiovascular training) Total Neuropathy Score—clinical version (TNSc), EORTC CIPN-20, functional assessment tools, disability, and QoL Reduction of CIPN symptoms and related functional and quality of life deficits. No changes in sensory or motor neurophysiologic parameters.
Schönsteiner et al. 2017 [89] Randomized exploratory phase 2 study (n = 131) - √ Whole-body vibration including massage, passive mobilization, and physical exercise. Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity subscale (FACT/GOG-NTX), EORTC QLQ-C30
Quantitative sensory testing (QST)		 Significantly and clinically relevant beneficial impact on symptom relief, physical fitness, and sensory function.
Schwenk et al. 2016 [90] Single blinded, randomized controlled pilot study (n = 22) - √ Interactive motor adaptation balance training program VPT score, numeric rating scale for pain (NRS), neuropathy-related numbness in feet (NRS score), Short-Form Health Survey (SF-12), Falls, Efficacy Scale-International (FES-I) Significant reductions in postural sway parameters in challenging semi-tandem position.
No significant changes were noted for balance with “eyes closed”, gait speed, and fear of falling.
Steinmann et al. 2011 in S3 clinical guidelineS3 Guideline Supportive therapy 2020 [37] Overview article √ √ Tactile Stimulation (e.g., been bath) Clinical improvement 81% of patients consider tactile stimulation to be very effective or effective.
Streckmann, Kneis et al. 2014 in
S3 Guideline Supportive therapy 2020 [37]		 RCT (n = 62) - √ Exercise (sensorimotor training, endurance, strength) QOL; coordination,
endurance, strength, therapy-induced side-effects.		 Due to the highly significant physiological parameters, the study was terminated prematurely.
Streckmann, Zopf et al. 2014 [60] Systematic review of RCTs (n = 10), CCT (n = 8) - √ Exercise interventions Side effects of Polyneuropathy Number of patients with reduced deep sensitivity could be diminished. Only one RCT related to CIPN.
S3 Guideline Supportive therapy 2020 [37] S3 Guideline - √ Non-drug methods Not described Sensorimotor training and whole-body vibration represent new options for CIPN treatment.
Clear evidence of improvement of functional limitation through non-medicinal procedures such as sports therapy, occupational therapy, physiotherapy, and physical therapy including electrotherapy.
Tofthagen et al. 2012 [96] Review of RCTs (n = 10), single-arm study (n = 1), cross-over-study (n = 1), quasi-experimental study (n = 1) - √ Strength training and balance training Neuropathy symptoms, strength, balance Recommendation of physical therapy as a treatment option, but no studies were identified that evaluate strength training and balance training for treatment of CIPN.
Zimmer et al. 2018 [94] RCT (n = 30) - √ Multimodal exercise program, (endurance, resistance, balance, coordination) Trial Outcome Index (TOI),NCI-CTC/FACT/GOG-NTX Regarding CIPN (TOI), there were significant differences between groups in the main analysis.
Consensus process N/A - √ Sugar oil peeling Clinical improvement CE 3
Consensus process N/A √ √ Tactile stimulation Clinical improvement CE 2–3
Mind-body therapies Brami et al. 2016 [16] Systematic review of RCTs (n = 13) - √ Mind-Body modalities NCV, Neurological Symptom Score, Total Neuropathy Score, QoL Evidence was reported for self-management strategies including yoga and mindfulness.
Galantino et al. 2019 [80] Open-label, single-arm, feasibility trial - √ Yoga, Meditation Functional Reach, Timed Up and Go, Patient Neurotoxicity Questionnaire (PNQ),
(FACT-GOG-NTX)		 Significant improvements were found in flexibility, balance, and fall risk.
Kanzawa-Lee et al. 2020 [54] Comprehensive inte-grative review(7 RCTs, 6 quasi-experimental studies) - √ Yoga, exercises CIPN, balance, and fitness Empirical evidence is insufficient to definitively conclude that exercise interventions ameliorate CIPN.
Nutritional therapy Brami et al. 2016 [16] Systematic review of RCTs (n = 13) √ √ Glutamine, Goshajinkigan, vitamin E, Omega 3, Acetyl-l-carnitine, Alpha-lipoic-acid NCV, Neurological Symptom Score, Total Neuropathy Score, QoL Vitamin E, Glutamine, Goshajinkigan, and Omega-3 may prevent CIPN.
Acetyl-l-carnitine may worsen CIPN; Alpha-lipoic-acid activity is unknown.
Greenlee et al. 2017 [42] Clinical practice guideline based on a systematic literature review of RCTs. √ √ Omega-3, fatty acids, vitamin E, alpha-lipoic acid, dietary modification - Acetyl-l carnitine is not recommended to prevent CIPN. Insufficient evidence that Omega-3, fatty acids, and vitamin E help to reduce neuropathy.
Rostock et al. 2013 [88] Four arm RCT (n = 60) - √ Vitamin B complex Detailed questionnaire, NRS Positive effects. No statistically significant results.
Hydrotherapy Consensus process N/A - √ Alkaline bath for hand/foot, then Aconit oil application Clinical improvement CE 3
Consensus process N/A - √ Cold knee and/or arm showers Clinical improvement CE 3
Acupuncture/Acupressure Brami et al. 2016 [16] Systematic review of RCTs (n = 13) - √ Electroacupuncture NCV, Neurological Symptom Score, Total Neuropathy Score, QoL Not superior to placebo.
Deng et al. 2013 [53] Systematic review of meta-analyses (n = 4), syst. Reviews (n = 14), RCT (n = 16) - √ Acupuncture VAS, neuropathy symptoms, QoL. Some improvement regarding VAS and neuropathy symptoms.
Donald et al. 2011 [68] Retrospective
Evaluation (n = 18)		 - √ Acupuncture CIPN symptoms. 82% (n = 14) reported improvement of neuropathy symptoms.
Greenlee et al. 2017 [42] Clinical practice guideline based on a systematic literature review of RCTs. √ √ Acupuncture, electroacupuncture - Insufficient evidence that electroacupuncture help to reduce neuropathy.
Rostock et al. 2013 [88] Four arm RCT (n = 60) - √ Electroacupuncture Detailed questionnaire, NRS Scale Positive effects. No statistically significant results.
S3 guideline complementary medicine in the treatment of oncology patients [57] S3 guideline - √ Acupuncture, electroacupuncture BPI, Total Neuropathy Score, NCS, Functional Assessment, QoL. Data are available from a meta-analysis and two RCTs on the efficacy of A- for CIPN.
Wong et al. 2016 [93] Prospective phase 2 study (n = 40) - √ Acupuncture like TENS Numbness score, mTNS, Edmonton Symptoms Assessment Scale (ESAS) Statistically significant difference at 6 months from the baseline pain score.
Cryotherapy Bandla et al. 2020 [18] Proof-of-concept study (n = 26) √ - Cryocompression Total neuropathy score (TNS), NCS Potentially improve efficacy of preventing CIPN. Safe and tolerable.
Beijers et al. 2020 [39] RCT (n = 180) √ - Frozen glove and sock CIPN20 Significant reduction of CIPN symptoms. Dropout of one-third of patients.
Griffiths et al. 2018 [19] RCT (n = 29) √ - Frozen glove and sock Neuropathic Pain Symptom Inventory, BPI. No significant differences in neuropathy or pain. Drop-out rate, more than 50 %.
Sundar et al. 2017 [40] Prospective pilot study (n = 20) √ - Continuous-flow limb hypothermia. Visual analog scale (VAS),
subjective tolerance scale, NCS, 		No significant difference in NCS. Well tolerated by all patients.
Consensus process N/A √ - Frozen gloves and socks Clinical improvement Cannot be assessed.
Manipulative therapies Brami et al. 2016 [16] Systematic review of RCTs (n = 13)) - √ Massage, touch therapy MD Anderson Symptom Inventory Greatly reduced CIPN symptoms from grade 2 to 1 and significantly improved quality of life.
Cunningham et al. 2011 [74] Case report - √ Massage MD Anderson Symptom Inventory Greatly reduced CIPN symptoms from grade 2 to 1 and significantly improved quality of life.
Izgu et al. 2019 [41] RCT (n = 40) √ Massage Self-Leeds Assessment of Neuropathic Symptoms and Sign (S-LANSS), EORCT QLQ CIPN20, NCS. Massage successfully prevented CIPN, improved the QoL, and showed beneficial effects on the NCS findings.
Sarisoy, et al. 2020 [76] RCT (n = 40) - √ Foot-massage VAS, Doleur Neuropatique/Neuropatic pain (DN4), Pittsburg Sleep Quality Index (PSQI) Positive effect on CIPN pain.
Schönsteiner et al. 2017 [89] Randomized exploratory phase 2 study (n = 131) - √ Whole-body vibration including massage, passive mobilization, and physical exercise. (FACT/GOG-NTX),
EORTC QLQ-C30
Quantitative sensory testing (QST)		 Significantly and clinically relevant beneficial impact on symptoms relieve, physical fitness, and sensory function.
Rhytmical embrocations Consensus process N/A - √ Aconit oil—rhythmical embrocation Clinical improvement CE 4
Consensus process N/A - √ Arnica comp/Formica oil—rhythmical embrocation Clinical improvement CE 4
TENS/Scrambler therapy Coyne et al. 2013 [67] Expanded trial, single arm trial (n = 39) - √ Scrambler therapy NRS, BPI, European Organization for Treatment and Cancer CIPN20 (EORTCCIPN20) Clinically important and statistically significant improvements were seen in average, least, and worst pain.
Gewandter et al. 2019 [65] Single-arm study (n = 29) - √ TENS EORTC-CIPN20, Utah Early Neuropathy Score Significant improvements were observed with the EORTC-CIPN20.
Loprinzi et al. 2020 [71] RCT, two arm phase II pilot trial (n = 50). - √ Scrambler therapy, TENS EORTC CIPN20, NAS questionnaire regarding CIPN-associated pain Scrambler therapy improves CIPN symptoms more than TENS.
Other supportive interventions Kotani et al. 2021 [43] Double-blind phase 2 trial (n = 56) √ - Compression Incidence of Grade ≥ 2 CIPN. No significant reduction of CIPN incidence.
Rostock et al. 2013 [88] Four arm RCT (n = 60) - √ Hydroelectric bath Detailed questionnaire, NRS Positive effects. No statistically significant results.
Consensus process N/A √ - Compression Clinical improvement Cannot be assessed.
Consensus process N/A - √ Copper ointment (0.4%) Clinical improvement E 2

Legend. 1 The number in brackets refer to the comprehensive reference list (see full article). 2 N/A: not applicable. 3 √: meets criteria; -: does not meet criteria, 4 CE = Clinical experience (rated on a numerical scale 0 to 5 with 0 = no effect and 5 = maximum effect.