Izgu, N., Ozdemir, L., & Bugdayci Basal, F. (2017). Effect of aromatherapy massage on chemotherapy-induced peripheral neuropathic pain and fatigue in patients receiving oxaliplatin: An open label quasi-randomized controlled pilot study. Cancer Nursing, 42, 139-147.

To explore the effects of aromatherapy hand/foot massage on chemotherapy-induced peripheral neuropathy (CIPN), pain incidence and severity, and fatigue severity, compared to standard care in GI cancer survivors who are actively receiving oxaliplatin

• Intervention: Aromatherapy hand/foot massage: ~40 minute sessions (10 minutes each hand/foot), 3 times per week, for 6 weeks (1-2 rest days between massages). Techniques included effleurage, light friction, and petrissage.
  •   Interventionist: the PI “qualified in massage therapy”
  •   Setting: Patients’ homes
  •   Essential oils: Chamomile, peppermint, and rosemary 1:1:1 blend in coconut oil made q72 hours ~2 ml applied to each hand/foot.
• Control condition: Standard care

• N = 46   
• AGE: 55.8 years (SD = 8.49) 
• MALES: 59%  
• FEMALES: 41%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Actively receiving FOLFOX6; primarily patients with colon cancer; stage of cancer unknown.
• OTHER KEY SAMPLE CHARACTERISTICS: Paresthesias rated ≥ 1 on NRS (range = 1-7); 2 (4%) patients had neuropathic pain at baseline per the DN4 cut-off; similar groups at baseline (including CIPN levels and dose/cycle of oxaliplatin received). Excluded patients with brain metastasis and preexisting neuropathy; whose oxaliplatin dose was reduced; and who were taking medication for neuropathy. 63% of eligible participants were recruited; 87% completed study. Two control group participants discontinued study due to fear of getting CIPN. 15% had received chemotherapy prior to their current FOLFOX regimen.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Ankara, Turkey: two university/research oncology hospitals

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Pilot, open-label, repeated measures, non-randomized, standard care-controlled quasi-experiment.

• Douleur Neuropathique 4 Questions (DN4): assessed patient self-reported neuropathic pain degree and presence via interview of neuropathic pain characteristics and association of pain with numbness, tingling, and itching; and clinical examination of painful area (hypoesthesia, pinprick, and allodynia). 
• Patient-report surveys: “Patient Questionnaire” (CIPN symptom location, aggravating factors, timing of peak severity, demographic, and clinical characteristics); 0-10 NRS (Current painful paresthesia severity-no pain to worst possible pain); Piper Fatigue Scale (PFS)
  • Timepoints of measurement: 
    • Baseline (before starting intervention)
    • At chemotherapy visits
      • ~mid-study (at 2 and 4 weeks)
      • ~post-intervention (6 weeks)
      • ~2 weeks postintervention completion (8 weeks)
  • Assessor: PI

• DN4: significantly lower CIPN neuropathic pain incidence in the intervention group (IG) than the control group (CG) at 6 weeks (p = 0.046), and severity at 4 and 6 weeks (p range = 0.006-0.027). 
• 0-10 NRS: significantly lower painful paresthesia severity after just one week in the IG than the CG (p ≤ 0.016). Median NRS scores remained a 3-4 at each follow-up (weeks 2-8), which was lower than the baseline score of 4.3, in the IG; but the NRS scores steadily increased from 4 at baseline to 5.5 at 8 weeks in the CG.
  • These effects (DN4 and NRS) did not last up to the 8-week timepoint.
• Piper Fatigue Scale (PFS): significantly lower fatigue levels at the 8-week timepoint in the IG than the CG (p = 0.036).

Aromatherapy hand/foot massage, using chamomile, rosemary, and peppermint oil, given 3 times per week for 40 minutes (10 minutes each hand/foot) during FOLFOX treatment may: 

• Transiently reduce the incidence and severity of CIPN neuropathic pain after 6 weeks, compared to standard care
• Help to treat or prevent the worsening of CIPN pain, as early as after one week of intervention; and fatigue long-term (2 weeks post a 6-week period of aromatherapy/massage treatment)

However, more rigorous RCTs with blinded assessors, utilizing larger sample sizes, are needed to evaluate the preventative and treatment effectiveness, necessary dosage, physiological mechanisms, and long-term effects of aromatherapy hand/foot massage on FOLFOX-induced CIPN pain.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• 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 validity/reliability questionable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Participants were recommended for the study by the med-oncs (sample bias); named as randomized, but procedures described a stratified but not randomized approach. PI was the massage therapist (unclear certification for massage therapy) and assessor of the primary outcome. Therapeutic interaction during massage could have contributed toward the intervention efficacy. Unspecified baseline assessment timing relative to chemotherapy infusion. Missing values were filled-in using the last-observation-carried-forward method. Mentioned a “primary education program” on page 5 with a very low completion rate, but this program was not mentioned elsewhere. No report of “Patient Questionnaire” outcomes. Measures were highly subjective. Intervention requires a certified aromatherapy/massage therapist able to travel to give 3 home visits of 40 minutes each. No control for potential moderators, such as mood/psychological well-being/coping.

Aromatherapy hand/foot massage during oxaliplatin treatment may be a safe and promising nonpharmacologic therapy for CIPN pain and fatigue. Further investigation of this therapy is warranted.