Ohno, T., Mine, T., Yoshioka, H., Kosaka, M., Matsuda, S., De Kerckhove, M., . . . Izumida, R. (2014). Management of peripheral neuropathy induced by nab-paclitaxel treatment for breast cancer. Anticancer Research, 34, 4213–4216.

To evaluate the effects of prophylactic compression therapy using stockings and sleeves combined with oral goshajinkigan, mecobalamin, and lafutidine on the prevention of nab-paclitaxel-induced peripheral neuropathy (PN)

The control and treatment groups received 260 mg/m² one time every three weeks from June 2012 to April 2013. Patients in the prophylactic treatment group wore stockings and sleeves from the beginning of nab-paclitaxel infusion, continuing for total of 24 hours. The treatment group also received prophylactic goshajinkigan (7.5 g per day), mecobalamin (1,500 mcg per day), and lafutidine (20 mg day) over the course of treatment. Assessments for side effects, including PN grade, were first conducted by a pharmacist then by a physician. If a subject proceeded to chemotherapy, a third set of tests were conducted by a nurse. For the treatment group, the nurse confirmed use of compression stockings and sleeves prior to chemotherapy.

• N = 14 
• AGE RANGE = 42–76 years
• MALES: Not provided, FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: Recurrent breast cancer; metastatic or locally advanced
• OTHER KEY SAMPLE CHARACTERISTICS: Previous treatment with taxanes; prior treatment lines; no other data provided

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: Nagasaki Harbor Medical Center, Nagasaki, Japan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care

Parallel-group trial

• National Cancer Institute'sCommon Terminology Criteria for Adverse Events (NCI-CTCAE)
• Various assessments for side effects including PN (not well described)

After the first cycle of chemotherapy, there was a significant difference in presence of PN (all grades) between groups. PN occurred in five out of seven subjects in the control group versus one out of seven subjects in the treatment group. The average grade of PN improved over cycles one through four in the treatment group.

In this small, nonrandomized trial, the grade of PN during one to four cycles of nab-paclitaxel therapy at 260 mg/m² was lower in the treatment group receiving compression therapy and prophylactic medications than the control group.

• Small sample (< 30)
• Baseline sample/group differences of import
• 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/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: This study had a small sample size, and sample characteristics were not well described. The design also was not well described, and there was no explanation of randomization techniques, inclusion and exclusion criteria, or measurements and methods. There was no explanation of baseline PN or the presence of other neurologic symptoms, and other medications previously or currently taken by participants were not reported. The total dose of ​nab-paclitaxel for both groups was not reported, and the mean dose of nab-paclitaxel was significantly greater in the treatment group with no explanation for this difference between samples. The total number of cycles completed for each group was not reported. There was no explanation of the method of administration for the prophylactic medication regimen. Compliance and tolerance rates were not reported. There was no report of any adverse side effects for the sample. The results reported appear incomplete and selectively done for the time period of collected data. Figure 1 depicting grade of neuropathy and number of cycles includes only four cycles for study period June 2012 to April 2013. Assumptions for statistical analysis not reported as met. There is a suggestion that this treatment supports the protection of peripheral nerves, but this assumption cannot be made based on this study as there is no discussion on the main effect on PN and the interaction of the combination of treatments in the treatment group. Citations are missing for the data reported in many places.

Combination prophylaxis with compression sleeves and stockings and medication (goshajinkigan 7.5 mg day, mecobalamin 1,500 mcg per day, and lafutidine 20 mg per day) needs additional investigation of its use for the treatment for nab-paclitaxel-induced PN. The safety, efficacy, benefit, and generalizability for appropriate target populations of this regimen also requires additional study in large, randomized, controlled trials. This study report had numerous flaws and limitations.