Effectiveness of physiotherapy interventions on improving quality of life, total neuropathy score, strength and reducing pain in cancer survivors suffering from chemotherapy-induced peripheral neuropathy – a systematic review

Figures & data

Figure 1. PRISMA flowchart for data extraction.

Table 1. A thorough review of various randomised control studies was included in the systematic review.

Sl. No.	Author and year of publication	Participants	Study setting	Inclusion criteria based on chemotherapy drugs and type & stage of cancer	Intervention	Duration of intervention	Outcome measures	Conclusion	Jadad scale score
1	Jana Muller et al. (2021) [15]	Total (n) = 170 with Age more than 18 years undergoing Neurotoxic Chemotherapy which were randomly allocated into three Groups Sensorimotor exercise training(n = 52), Resistance Training (n = 60), Usual Care (n = 58)	Inpatient, supervised	(1)Taxanes based, Taxane – Platinum combination, Platinum-Based, Vinca Alkaloid, Platinum - Vinca Alkaloid Combination (2) All Types of Cancer (3) Stage I, II, III, IV	(1) Sensorimotor Exercise Training (SMT) (2) Resistance Training (RT) (3) Usual Care (UC)	3 days per week for a total of 105 min/week during neurotoxic chemotherapy (mean length: 20 weeks)	(1) Total Neuropathy Score (2) EORTC QLQ-CIPN15 questionnaire.	This study shows that, when given the right training stimulus, SMT and/or RT can reduce subjectively experienced sensory CIPN symptoms in the feet as well as other clinically significant cancer therapy-related outcomes.	3
2	Neirman Yukselturk Simsek et al. (2021)[16]	Total Participants were n = 90 and randomised into three groups exercise, cold application, Control with 30 participants in each group	Home-based Exercise, Supervised	(1) Taxanes chemotherapy (2) Breast cancer (3) Stage II, III and IV	A progressive strengthening, stretching, and balance exercise programme was used. Use of cold packs, which were then continued at home. Patients in the control group received standard medical care according to the clinic’s protocols.	5 times a week for 12 weeks with sessions lasting 15 to 20 min	TNS (2) CIPNAT	In the management of CIPN, it was discovered that exercise was more effective than cold application.	3
3	Peter A. Argenta et al. (2020) [16]	Total participants were n = 79 divided into groups Control (n = 28) and experiment Group (n = 51)	Outpatient rehabilitation	(1) Oxaliplatin (2) All types of Malignant Tumour (3) Stage IV	Gymnastics instruction and rapid walking. Comprehensive gymnastics training. Quick-step walking training (according to the patient’s own physical capabilities).	2 weeks Rehabilitation Program	(1) FACT/GOG/Ntx (2) Functional Test (3) Brief Pain Inventory Scores	Exercise rehabilitation programmes were beneficial at treating CIPN which was related to chemotherapy cycles and cumulative doses.	1
4	Si- Yeon Song et al. (2020) [23]	Total Participants were n = 72, Randomly allocated into Electrostimulation Group (ES) (n = 36) and Sham Electrostimulation group (SES) (n = 36)	Home Based Program	(1) Not specified (2)Breast Cancer (3) Stage Not Specified	Low-frequency ES was given through medical to treat CIPN symptoms. Despite not producing an electrical stimulus, the sham gadget had a similar appearance to the real one. For blinding, the labels on the interventional and placebo devices were identical (100 µA, 40 Hz) .	2 times a day for 120 min with minimum 1 h without interruption for 2 weeks	(1) NRS (2)TNS (3)EQRT-QLQ (4)CIPN 20 (5) FACT-B (6)IPIE -CIPN	The low-frequency ES device with pharmaceutical intervention was not substantially more effective than a placebo, yet a therapeutic impact was feasible.	5
5	Elizabeth Anderson Hammond et al. (2020)[17]	Total participants (n = 60) randomly allocated into treatment group (n = 28) and Control Group (n = 32)	Home-based Exercise Program	(1) Taxanes Chemotherapy (Docetaxel, Cyclophosphamide, Flurouracil, Epirubian) (2) Breast Cancer (3) Stage I, II and III	Nerve gliding exercises were the Main component of the home exercise program.	3 times for 5 − 10 min for 6 months	1)NPRS 2)DASH 3)S-LANSS 4)Vibration Analysis 5)Pressure Algometry 6) Grip Strength - Hand Held Dynamometer	Home physical therapy programmes found to reduce CIPN pain in the upper extremity, and maintain a healthy weight while receiving chemotherapy were found to be associated with the preservation of sensory function.	3
6	Shelly Dhawan et al. (2019)[18]	Total Participants n = 45, Allocated randomly into Exercise Group (n = 22) and usual care group (n = 23)	Home-based exercise program	(1) Paclitaxel and carboplatin (2) All types of cancer	The Intervention Group Received Muscle Strengthening and Balance exercises	10 weeks for 30 min per day	(1) Nerve conduction velocity (2) S-LANSS (3) EORTC QLQ-CIPN15 questionnaire	Exercises that balance and strengthen muscles are useful for lowering CIPN pain and enhancing cancer patients’ quality of life.	2
7	Kelcey A. Bland et al. (2019) [19]	Total Participants were n = 31 randomised into two groups Immediate Exercise (n = 15) and Delayed Exercise (n = 16)	Outpatient, supervised intervention	(1) Taxanes chemotherapy (2) Breast cancer (3) Stage I, II and III	Resistance training, starting with one set of 10 repetitions at 50% of the estimated one repetition maximum and progressing to two sets of 10 to 12 repetitions at 65% of the estimated one repetition maximum.	3 Days a week for 8 to 12 weeks	(1) EORTC QLQ-CIPN30 questionnaire (2)Chemotherapy Completion Rate	Exercising may reduce CIPN during taxanes chemotherapy and perhaps increase taxane adherence in breast cancer patients. These results need to be validated in larger trials, as well as whether exercise can lessen CIPN by confirming the findings of taxanes chemotherapy.	3
8	S. Kneis et al. (2019) [20]	Total Participants n = 50, Allocated into Intervention Group (IG) (n = 25) and control group (CG) (n = 25)	Outpatient, Supervised Intervention	(1) Breast, colorectal, gynaecological cancer, upper gastrointestinal non-small cell lung cancer, Non-Hodgkin’s lymphoma, multiple myeloma	Both groups were engaged in endurance training on stationary bicycles for up to 30 min at a moderate intensity below their own anaerobic thresholds. Additionally, for 30 min, the IG practised balance.	2 days a week for 12 weeks. Each session lasted for 30 min	Balance performance, jumping performance, vibration sense, quality of life (EORTC QLQ-CIPN15 questionnaire and FACT/GOG-Ntx), patient-reported CIPN symptoms	Balance training improved patients’ functional status, endurance training also caused a decrease in sensory problems in both groups. Improved performance on the CIPN20 motor score. Both activities offer CIPN sufferers a distinct and useful advantage.	3
9	Ian R. Kleckner et al. (2018) [21]	Total Participants were(n = 420) randomly divided into 2 groups only Exercise (n = 231) and Control Group (n = 225)	Home-based Exercise Program, Unsupervised	(1) Taxanes based, Taxane - Platinum combination, platinum-based, vinca alkaloid, platinum - vinca alkaloid combination (2) All types of cancer (3) Stage I, II, III, IV	(1) Exercise Group – Walking Prescription with 60 to 85% Heart Rate Reserve and Strengthening using theraband. (2) Control group - Received only chemotherapy	5 days in Week for 6 weeks with 60 min sessions each day	Self-reported CIPN symptoms of hot/coldness in hands/feet and numbness and tingling.	Patients undergoing treatment based on taxanes, platinum, or vinca alkaloids appear to experience fewer CIPN symptoms after exercising. Clinicians ought to think about advising these patients to exercise.	2
10	Philipp Zimmer et al. (2017) [22]	Total participants −30 with Stage 4 cancer undergoing outpatient treatment Chemotherapy and were randomly allocated to the Intervention Group (n = 17) and control Group (n = 13)	Outpatient Intervention Group received Supervised Intervention	(1) Oxaliplatin Based Chemotherapy (2) Metastasized Colorectal Cancer (3) Stage IV	(1) Intervention Group received Supervised intervention in three phases where Phase I -balance training and coordination practice, Phase II - Endurance and Resistance training and Phase III - Cool Down Period (2) Control Group received a written recommendation for fitness	2 days a week for 8 weeks. Each session lasted for 60 min	(1) Quality of life was assessed using FACT/GOG-NTX (2) Physical Measures (Balance, Dynamic Muscular Strength, and Endurance) Endurance was assessed using 6 min Walk Test	In a palliative situation, this study is the first to demonstrate the beneficial effects of a multimodal exercise programme on CIPN, balance, and strength in patients with metastatic colorectal cancer. The findings confirm past findings that balancing has a beneficial effect on chemotherapy-induced peripheral neuropathy symptoms	2

SMT: sensorimotor training; CIPN: chemotherapy-induced peripheral neuropathy, EORTC-QOL: European Organisation for the Research and treatment of cancer quality of life questionnaire; RT: resistance training; TNS: total neuropathy score; CIPNAT: chemotherapy-induced peripheral neuropathy assessment tool; FACT/GOG/NTX: functional assessment of cancer therapy –gynecologic oncology group- neurotoxicity; ES: electrostimulation, NRS: numerical rating scale, FACT: B- functional assessment of cancer therapy – breast; IPIE: instrument on pattern identification and evaluation; NPRS: numerical pain rating scale; DASH: disabilities of arm, shoulder and hand; LANSS: Leeds assessment of neuropathic pain scale.

Table 2. Critical appraisal of each article using PEDro (physiotherapy evidenced database) scale.

SR No.	Study	1 (not Included in score)	Rating for the criterion										Total score	Main concerns
			2	3	4	5	6	7	8	9	10	11
1	Jana Muller et al. (2021) [24]	✓	✓	✗	✓	✗	✗	✓	✓	✓	✓	✓	7	No concealed allocation and no masking (Blinding)
2	Neirman Yukselturk Simsek et al. (2021) [15]	✓	✓	✗	✓	✗	✗	✗	✓	✗	✓	✓	5	No blinding and there was no concealed allocation and lack of intention to treat analysis
3	Peter A. Argenta et al. (2020) [16]	✓	✗	✗	✓	✗	✗	✗	✓	✓	✓	✓	5	There was no random allocation and concealed allocation. No masking
4	Si- Yeon Song et al. (2020) [23]	✓	✓	✓	✓	✗	✓	✓	✓	✓	✓	✓	9	The therapist was not blinded
5	Elizabeth Anderson Hammond et al. (2020)[17]	✓	✓	✓	✓	✗	✗	✓	✓	✗	✗	✓	6	No blinding of therapist and participants, There was no Adequate follow up and lack of intention to treat analysis
6	Shelly Dhawan et al. (2019) [18]	✓	✓	✓	✓	✗	✗	✗	✓	✓	✓	✓	7	No blinding
7	Kelcey A. Bland et al. (2019) [19]	✓	✓	✓	✓	✗	✗	✗	✓	✗	✓	✓	6	There was no blinding and there was a lack of intention to treat
8	S. Kneis et al. (2019) [20]	✗	✓	✓	✓	✗	✗	✗	✗	✓	✓	✓	6	Eligibility criteria were not adequately specified and No Masking and no adequate follow up
9	Ian R. Kleckner (2018) [21]	✗	✓	✓	✓	✗	✗	✗	✗	✓	✓	✓	6	Eligibility criteria were not adequately specified and No Masking and no adequate follow up
10	Philipp Zimmer et al. (2017)[22]	✓	✓	✗	✓	✗	✗	✗	✓	✓	✓	✓	6	No concealed allocation and No masking (Blinding)

1: Eligibility criteria, 2: Random allocation, 3: Allocation concealment, 4: Baseline outcome measurement of groups, 5: Blinding of participants, 6: Therapist blinding, 7: Assessor blinding, 8: A measure of key outcomes obtained from more than 85% of subjects initially allocated, 9: Intention to treat analysis, 10: Between-group statistical comparisons are reported, 11: Point measures and measures of variability of any one outcome.

Şimşek NY, Demir A. Cold application and exercise on development of peripheral neuropathy during taxane chemotherapy in breast cancer patients: a randomized controlled trial. Asia Pac J Oncol Nurs. 2021;824(3):255–266. doi: 10.4103/apjon.apjon-2075.

 Google Scholar

PA A, KV B, MA G, et al. The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: a randomized, sham-controlled clinical trial. Gynecol Oncol. 2017;144(1):159–166.

 PubMed Web of Science ®Google Scholar

Song S-Y, Park J-H, Lee JS, et al. A randomized, placebo-controlled trial evaluating changes in peripheral neuropathy and quality of life by using low-frequency electrostimulation on breast cancer patients treated with chemotherapy. Integr Cancer Ther. 2020;19:1534735420925519. doi: 10.1177/1534735420925519.

 Web of Science ®Google Scholar

Andersen Hammond E, Pitz M, Steinfeld K, et al. An exploratory randomized trial of physical therapy for the treatment of chemotherapy-induced peripheral neuropathy. Neurorehabil Neural Repair. 2020;34(3):235–246.

 PubMed Web of Science ®Google Scholar

Dhawan S, Andrews R, Kumar L, et al. A randomized controlled trial to assess the effectiveness of muscle strengthening and balancing exercises on chemotherapy-induced peripheral neuropathic pain and quality of life among cancer patients. Cancer Nurs. 2020;43(0 ):269–280.

 Google Scholar

Bland KA, Kirkham AA, Bovard J, et al. Effect of exercise on taxane chemotherapy-induced peripheral neuropathy in women with breast cancer: a randomized controlled trial. Clin Breast Cancer. 2019;19( 6):411–422.

 PubMed Web of Science ®Google Scholar

Kneis S, Wehrle A, Müller J, et al. It’s never too late – balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial. BMC Cancer. 2019;19( 1):414.

 PubMedGoogle Scholar

Kleckner IR, Kamen C, Gewandter JS, et al. Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial. Support Care Cancer. 2018; 26( 4):1019–1028.

 PubMed Web of Science ®Google Scholar

Zimmer P, Trebing S, Timmers-Trebing U, et al. Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves balance and strength in metastasized colorectal cancer patients: a randomized controlled trial. Support Care Cancer. 2018;26( 2):615–624.

 PubMed Web of Science ®Google Scholar

Müller J, Weiler M, Schneeweiss A, et al. Preventive effect of sensorimotor exercise and resistance training on chemotherapy-induced peripheral neuropathy: a randomised-controlled trial. Br J Cancer. 2021;125(7):955–965.

 PubMed Web of Science ®Google Scholar

Data availability statement

The data that support the findings of this study are openly accessed and available in PubMed, Cochrane Library, Embase and Pedro