Kurt, S., & Can, G. (2018). Reflexology in the management of chemotherapy induced peripheral neuropathy: A pilot randomized controlled trial. European Journal of Oncology Nursing, 32, 12–19.

To test the effects of reflexology on chemotherapy-induced peripheral neuropathy (CIPN), compared to standard care and CIPN education alone, in cancer survivors who have grade II-IV peripheral neuropathy.

Standard care control: All participants received verbal education and a brochure on CIPN at baseline, and standard care. 

Intervention: (a) same CIPN verbal education and brochure; (b) reflexology: rhythmic massaging of the head, neck, feet/toes, and fingers applied by a certified reflexologist or a family member trained by the reflexologist. Duration is 20 minutes, twice per day, for six weeks.

• N = 60 (30 in intervention group; 30 in control group)
• AGE: 58 years
• MALES: 53%  
• FEMALES: 47%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Had (a) grade II-IV (mostly grade II) peripheral neuropathy at baseline and had been referred for a neurology examination by their physician; (b) CIPN duration consistent in 68% of patients; (c) received any chemotherapy regimen (mostly taxane- or oxaliplatin-based) and an average of about seven chemotherapy agents; and (d) any cancer type (mostly breast or gastrointestinal cancers). Cancer treatment status unknown. 
• OTHER KEY SAMPLE CHARACTERISTICS: Nearly all patients (93%) had stopped work due to their present illness. Less than 30% completed secondary school or higher. Most (92%) were married.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Trakya University Balkan Oncology Hospital in Edirne, Turkey

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care

Pilot randomized controlled trial

• Measurement time points: baseline (before the intervention), three weeks (midpoint), and six weeks (intervention completion).
• Brief Pain Inventory (BPI)–Patient-reported outcome (PRO) measure of pain severity and pain interference with general activities (e.g., walking, sleep, enjoyment of life).
• European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherpay-Induced Peripheral Neuropathy Form (EORTC QLQ-CIPN20)–PRO measure of sensory, motor, and autonomic CIPN symptoms
• NCI CTCAE v4.0–Physician-graded scale of neurotoxicity.
• Neurologic examination–Conducted by physician (only at baseline and six weeks)

Pain interference (BPI), and CIPN motor and autonomic symptoms (EORTC QLQ-CIPN20) improved from baseline to sixweeks in the reflexology group (p ≤ 0.017); but no difference was found between groups at any time point. In the reflexology group, sensory CIPN (EORTC QLQ-CIPN20) improved from baseline to six weeks (p < 0.001) and was significantly less severe at the six-week time point than the standard care group (p = 0.024). The control group’s pain/CIPN severity scores also decreased (non-significantly) over time.

Although reflexology may provide some benefit and relief for cancer survivors with peripheral neuropathy, this study does not support its efficacy in treating CIPN.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Patient’s current cancer treatment status was unclear; participants could have had peripheral neuropathy from other causes; not all participants received neurotoxic chemotherapy; other CIPN-influencing factors were not controlled for (e.g., diabetes status, concomitant CIPN treatments); sample and eligibility criteria was poorly described; unclear measurement methods–unclear whether patients were interviewed or individually responded to the questionnaires; if interviewed, unclear if the interviewer was blinded; no results reported for the NCI CTCAE v4.0 measure, neurologic exam, or BPI pain severity items; measurement or control for potential contamination, compensatory intervention (by the patients’ doctors), or issues with fidelity; unclear how family members were trained and checked-off to perform the intervention; unclear how many reflexology sessions were conducted by the reflexologists versus the family members, and whether this number was standardized across participants; unclear how they measured patient/family member’s adherence to the protocol; simple (assumed to be convenience) sampling used; Mann Whitney u and Wilcoxon ranked tests were used instead of a repeated measures ANOVA or other more powerful statistical test.

This study suggests reflexology could help to reduce CIPN severity; however, it had several critical limitations. Further research is needed to rigorously evaluate the effects of reflexology on specific types and symptoms of CIPN (e.g., taxane-induced chronic painful CIPN versus oxaliplatin-induced non-painful CIPN)—controlling for key CIPN-influencing factors such as participants’ phase of chemotherapy treatment; baseline CIPN duration, stability, and severity; functional status; concomitant CIPN treatments (e.g., duloxetine); and peripheral neuropathy-related comorbidities—in diverse populations. Subsequently, research is needed to evaluate the specific doses of and mechanisms by which reflexology reduces and/or prevents CIPN.