Kono, T., Hata, T., Morita, S., Munemoto, Y., Matsui, T., Kojima, H., . . . Mishima, H. (2013). Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): A phase 2, multicenter, randomized, double-blind, placebo-controlled trial of goshajinkigan to prevent oxaliplatin-induced neuropathy. Cancer Chemotherapy and Pharmacology, 72, 1283–1290.

To evaluate the efficacy of a Japanese medicine called goshajinkigan (TJ-107) for preventing oxaliplatin-induced neuropathy, compared to placebo controls, and also to evaluate its safety

Patients were randomized to receive goshajinkigan ( TJ-107) 7.5 mg per day day, a mix of extracts of 10 crude herbs, or placebo for 26 weeks starting on the first day of chemotherapy. Neuropathy was measured before each chemotherapy cycle every two weeks until the eighth chemotherapy cycle and every four weeks thereafter until 26 weeks. Patients randomly were assigned to the intervention or control group.

• N = 89
• MEDIAN AGE = 64 years
• AGE RANGE = 36–88 years
• MALES: 53.9%, FEMALES: 41.6%
• KEY DISEASE CHARACTERISTICS: To be included in the study, patients had to be undergoing oxaliplatin-based chemotherapy for colorectal cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Primarily Eastern Cooperative Oncology Group score of 0 upon enrollment

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Japan

• PHASE OF CARE: Active treatment
• APPLICATIONS: Palliative and supportive care

• Double-blinded, randomized, placebo-controlled trial

• Neuropathy was measured by National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) sensory items at baseline and every two weeks until the eighth cycle of chemotherapy and monthly until the 26th week.
• The FACT/GOG-NTX-12 also was completed by patients at baseline and before every chemotherapy cycle.

Although there was a trend toward lower neuropathy scores as measured by the FACT/GOG-NTX in the intervention group at eight weeks (p = .421) and 26 weeks (p = .151), the differences were not statistically significant. The incidence of grade 2 peripheral neuropathy or greater until the eighth cycle was 39% in the experimental group and 51% in the control group (RR = 0.76, 95% CI 0.47–1.21), and the incidence of grade 3 or greater neurotoxicity was 7% in the treatment group and 13% in the placebo group (RR = 0.51, 95% CI 0.14–1.92). The time to development of grade 2 or greater toxicity was 5.5 months in the experimental group and 3.9 months in the placebo group (RR = 0.65, 95% CI 0.36–1.17). No differences were observed between those getting the different FOLFOX regimens. The goshajinkigan was tolerated well. Adverse effects were similar between study groups and most likely caused by the chemotherapy, but vomiting was significantly less prevalent in the treatment group (p = .029).

Goshajinkigan may delay development of grade 2 or greater oxaliplatin-induced peripheral neuropathy, and there was a trend toward less severe chemotherapy-induced peripheral neuropathy in the intervention group at 8 and 26 weeks as compared to the control group.

• Small sample (less than 100)
• Findings not generalizable
• Other limitations/explanation: Not generalizable to people with neuropathy caused by any other drug than oxaliplatin

This study showed that administration of goshajinkigan, a traditional Japanese kampo medicine, was associated with reduced prevalence and severity of neurotoxicity among patients receiving oxaliplatin and was tolerated well by patients. Further study is needed to support the use of goshajinkigan for oxaliplatin-induced peripheral neuropathy. Goshajinkigan may not be widely available in the United States or outside of Japan.