Han, X., Wang, L., Shi, H., Zheng, G., He, J., Wu, W., . . . Wei, G. (2017). Acupuncture combined with methylcobalamin for the treatment of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma. BMC Cancer, 17, 40.

To investigate if acupuncture plus methlycobalamin is an effective treatment compared to methlycobalamin alone in reducing CIPN in patients with multiple myeloma.

Acupuncture plus methylcobalamin (Met + Acu) was compared with methylcobalamin alone to evaluate effectiveness on CIPN as measured by VAS, FACT-GOG-NTX (functional assessment of neurotoxicity) and nerve conduction velocity compared to methlycobalamin (Met) alone in patients with multiple myeloma.

Patients with multiple myeloma randomized to treatment group (Met+Acu) or control group (Met). Intervention duration for both groups was 84 days
                                               
Methylcobalamin administration protocol x 3 cycles/84 days: 1 cycle = 500 mcg IM qod x 20 days(10 injections) then two months oral met 500 mcg tid                                                                                                                                                                                           

Acu administration of protocol x 3 cycles: 1 cycle = bilateral acupuncture needles at designated acupoints (aseptic adm by senior physician (15 years of experience) at depth 0.3-1 inches x 30 minutes; initially in prone position with needle retention then administered to same acupoints in supine position x 3 days then qod x 10 days

• N = 98  (49 in treatment, 49 in control group) 
• AGE: Mean = 64 years
• MALES: 57%  
• FEMALES: 43%
• CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Multiple myeloma: subtypes IgG, IgA, IgD, light chain (kappa/lamda)
• OTHER KEY SAMPLE CHARACTERISTICS: Baseline EMG showed impairment of median and peroneal nerve conduction, no central nervous system or other disease related preexisting peripheral neuropathy, no pre-chemo peripheral neuropathy; baseline PN occurring after initiation of chemotherapy assessed by NCI-CTCAE at grade 2-4; baseline VAS 5.5-5.57/10; baseline FACT/GOG-NTX scores 36.48-36.63; no significant differences in baseline characteristics between treatment and control group.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Multiple Myeloma Center, Bone Marrow Transplantation Center, Department of Hematology: The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

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

Prospective randomized controlled trial to investigate effect of Met + Acu versus Met on CIPN, sx neurotoxicity and nerve conduction

VAS pain score (neuropathic pain); FACT/GOG-NTX questionnaire (functional assessment of neurotoxicity); EMG (nerve conduction velocity)

Evaluated outcome measures before and after treatments within and between Met + Acu and Met groups:

• VAS decreased in both Met + Acu and Met group (p < 0.001); Significant decrease VAS in Met + Acu compared to Met control group (p < 0.01)
• FACT/GOG-Ntx scores significant improvement within Met + Acu group (p < 0.001) and between Met + Acu group compared to Met control group (p < 0.05)
• Nerve conduction velocity: Motor conduction velocity significant improvement in Met + Acu group of bilateral median (p < 0.05) and peroneal nerves (p < 0.01); sensory conduction velocity showed significant improvement within Met + Acu group and between Met + Acu and Met control group of only sural nerve (p < 0.01); No improvement in FACT/GOG-NTX scores or in nerve conduction velocity in Met control group.

In 98 patients with multiple myeloma with grade 2 or higher CIPN, there was significant reduction in PN pain in Met + Acu and Met groups but more significant relief with Met + Acu. Only Met + Acu group had significant improvement in functional assessment of neurotoxicity symptoms and nerve conduction; no improvement in Met control group

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no appropriate attentional control condition) 
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Other limitations/explanation: CIPN grade using NCI-CTCAE was not re-evaluated after baseline; CIPN severity assessment not reported and used a different grading system than baseline; randomization procedures not explained; sampling methods not described, uncertain whether VAS was specific to neuropathic pain in the hands/feet or general pain; FACT/GOG-NTX instrument validated for platinum/paclitaxel-induced peripheral neuropathy, and findings of specific categories of FACT/GOG-NTX not reported; only combined scores (this instrument measures peripheral neuropathy on multiple dimensions physical, social, emotional, functional, neurotoxicity sx); Actual p values not reported; no effect size reported; a two-way ANOVA should have been used to compare within- and between-group differences, an independent sample t test was used for the same group when a paired t test should have been used; prior/current treatment regimens of sample not identified to determine distinct pharmacologic origin of CIPN; not specified if patients actively receiving treatment or off treatment or time from last treatment; analgesics/neuroleptics/other CIPN treatments prior to or during study not identified, prior acupuncture (i.e., contamination) not identified

Acupuncture plus methylcobalamin may relieve CIPN-related pain, function, and nerve conduction in patients with multiple myeloma. Large multi-center, randomized controledl trials are needed to validate these findings and investigate their effects related to pharmacotherapies specific to MM utilizing rigorous measurement tools and validated instruments specific to patients with MM.