Oki, E., Emi, Y., Kojima, H., Higashijima, J., Kato, T., Miyake, Y., . . . Maehara, Y. (2015). Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): A placebo-controlled, double-blind, randomized phase III study. International Journal of Clinical Oncology, 20, 767–775. 

To evaluate the effectiveness of goshajinkigan (GJG) in reducing peripheral neurotoxicity in patients receiving FOLFOX for colorectal cancer

Patients with colorectal cancer were randomized to receive either GJG 7.5 mg three times daily or placebo in a double-blind manner. The time to grade 2 or higher neuropathy was the primary endpoint.

• N = 155 (of planned 310)   
• MEAN AGE = 62.4 years (GJG), 60.4 years (placebo)
• MALES: 53.9% (GLG), 54.8% (placebo); FEMALES: 46.1% (GLG), 45.2% (placebo)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All patients had stage III colorectal cancer. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Most patients had no comorbidities.
• OTHER KEY SAMPLE CHARACTERISTICS: Creatinine clearance greater than 60 in 86.5% of patients receiving GJG; 90.3% of patients receiving placebo

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

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, randomized study

Time to grade 2 or higher neuropathy as described by Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, and the DEB-NTC. Standardized questions regarding symptoms of neurotoxicity and examples of answers were used to facilitate accurate classification and grading of symptoms. Grades were determined by physicians and were documented in patient records.

A total of 142 patients were evaluable. Incidence of grade 1 peripheral neuropathy was 43.8% in the GJG group and 62.4% in the placebo group; incidence of grade 2 or higher was 50.6% in the GJG group and 31.2% in the placebo group. Time to development of neuropathy was also significantly less in the GJG group (p = 0.007). GJG did not reduce time to neuropathy even for grade 1. Adverse events other than neuropathy showed no difference between the two groups. Secondary endpoints of dose intensity and treatment cycle were higher in the GJG group (not significant).

GJG did not decrease the time to grade 2 neuropathy; in fact, it seems to have hastened development. There was some effect on the dose intensity and treatment cycle given, but this was not a significant difference.

• Key sample group differences that could influence results
• The study stopped early because of findings that it was not effective in the manner theorized.

A total of 155 patients in each arm were planned, but after a total of 155 patient enrolled, an interim analysis was performed and the study was stopped at that time because of findings that GJG was not as effective as hoped. Nurses must ask patients medications, including all supplements, to educate patients on potential interactions and potential harm from supplemental medications. This is marketed in Japan for treatment for diabetic neuropathy but does not seem to be effective for chemotherapy-induced neuropathy, and education of patients is key.