Abe, H., Kawai, Y., Mori, T., Tomida, K., Kubota, Y., Umeda, T., & Tani, T. (2013). The Kampo medicine Goshajinkigan prevents neuropathy in breast cancer patients treated with docetaxel. Asian Pacific Journal of Cancer Prevention, 14, 6351–6356.

To evaluate the effects of ​goshajinkigan (GJG) compared to vitamin B12 on the incidence of docetaxel (DOC)-associated peripheral neuropathy (PN) in chemotherapy-naïve patients with breast cancer

Patients were stratified by type of chemotherapy and age for randomization by dynamic allocation (balanced marginal distribution of stratification factors) then randomly assigned to receive either GJG (7.5 g per day orally divided into two to three doses before or between meals during DOC therapy) or B12 (1,500 mcg per day orally after meals daily during DOC therapy). A baseline evaluation of adverse effects was completed on days 1 and 8 by nurses. using the Neurotoxicity Criteria of Debiopharm (DEB-NTC), the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), and a Visual Analog Scale (VAS) for pain. The VAS for pain was completed again after DOC chemotherapy. The study continued as long as DOC treatment or for six cycles. Patients were premedicated with 5-HT receptor antagonists and corticosteroids. A granulocyte-colony stimulating factor (filgrastim or lenograstim) was administered if a patient's neutrophil was less than 500/mcL or if febrile neutropenia occurred. Chemotherapy regimens included TC (DOC 75 mg/m² and cyclophosphamide 600 mg/m² for three weeks for four cycles), single-agent DOC (DOC 100 mg/m² for three weeks for four cycles), and XT (capecitabine 900 mg/m² PO BID on days 1–14 and DOC 60 mg/m² for three weeks for six cycles). Patients receiving HER-2 therapy received trastuzumab before chemotherapy.

• N = 57
• MEDIAN AGE = 58 years (range = 33–70 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer stages I, IIa, IIb, and III

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: Shiga University of Medical Science Hospital, Shiga, Japan

• PHASE OF CARE: Active antitumor treatment

Prospective, randomized, parallel-group trial

• Neurotoxicity Criteria of Debiopharm (DEB-NTC)
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE v3.0)
• Visual Analog Scale (VAS) for pain

The incidence of PN was significantly lower in the group receiving GJG (39.3%) compared to the group receiving B12 (88.9% [p < 0.01]). The incidence of grades 2 and 3 PN were significantly lower in the group receiving GJG compared to the group receiving B12 (DEB-NTC = p < 0.01 and NCI-CTCAE p < 0.01). The mean VAS score was significantly lower in the group receiving GJG (2.7 + 2.2) versus B12 (4.9 + 2.4 [p = < 0.01]). There were no significant differences in characteristics between the groups. The completion rate and recommended dietary intake percent were similar for the GJG and B12 treatment groups. The total dose of DOC was 338.5 mg/m² in the GJG group versus 340 mg/m² in the B12 group.

The findings of this study suggest that GJG might be helpful in the prevention of PN in patients receiving chemotherapy regimens that include DOC. However, additional research to develop strong evidence in this area is needed.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Findings not generalizable
• Other limitations/explanation: There was a reporting discrepancy in which N = 57 patients enrolled in results, but the data report n = 33 in the GJG group and n= 27 in the B12 group, totaling 60 patients. There is no explanation for drop-outs or missing data. There was no placebo control group receiving only chemotherapy. There was no explanation of the study's timeframe. The VAS was completed at baseline and after DOC chemotherapy, but the methods of assessment not well described. The study included conflicting reports of patient characteristics, stating that 16% of patients received neoadjuvant chemotherapy even though this was stated as an exclusion criterion. It was unclear whether the total DOC dose between groups was significant. It was reported that there was no difference between groups regarding other toxicities, but the data displayed frequencies not of significance with the chi square P value. There was no report regarding the timeframe of PN onset or occurrences during treatment between groups. The use of B12 was reported as increasing the incidence of neurotoxicity, yet no control group existed as a frame of reference to make this assumption. A break-down of the data differences in the PN scales used (NCI-CTCAE and DEB-NTC, sensory severity/impairment and duration) was not provided. The definitions of grades are different between the two scales.

GJG at 7.5 g per day orally divided into two to three doses before or between meals may be beneficial to reduce incidence and severity of PN in patients with breast cancer receiving first-time DOC regimens. The safety and efficacy of this treatment need to be validated in larger randomized, controlled trials that compare GJC to placebos and use other assessment instruments.