Preventive Effect of Goshajinkigan Against Peripheral Neuropathy Induced by Paclitaxel-Containing Chemotherapy: an Open-Label, Randomized, Phase II Study.

TPS12141 Background: Paclitaxel is a taxane agent that has been used as a standard treatment for various malignancies. However, taxanes, such as paclitaxel, unfortunately cause a high frequency of chemotherapy-induced peripheral neuropathy (CIPN) as a result of axonal damage (All grade; 70%) (Clin Cancer Res.1996), CIPN worsens patients’ QOL and then lead to poor treatment compliance. Furthermore, there is no evidence for the prevention of CIPN. Goshajinkigan (GJG) is one of the Kampo medicine and it is approved in Japan for the treatment of numbness and has been commonly used for diabetic peripheral neuropathy. In addition, a non-clinical study has also shown the preventive effect of GJG against CIPN induced by paclitaxel (Molecular pain. 2014). To investigate if GJG indeed has a preventive effect for severe CIPN in patients receiving chemotherapy including paclitaxel, we started a two-arm randomized trial of GJG vs physician’s choice of treatment for patients. Methods: Patients have to meet the followings: pathologically diagnosed with malignant tumor (regardless of cancer type) and scheduled to receive ≥4 courses of chemotherapy including carboplatin and paclitaxel (paclitaxel ≥150mg/m2 every 3-4 weeks) as initial chemotherapy; age ≥20yrs; Performance Status of 0 or 1. The primary endpoint is set as a proportion of ≥G2 CIPN by CTCAE ver.5.0 by the end of 4 courses of chemotherapy. With stratification by cancer type and age, patients will be randomized centrally to receive GJG at the same time as chemotherapy (A), or to receive the physician’s choice of treatment for pts if ≥G2 CIPN occurs without prophylaxis (B). Assuming that the incidence of ≥G2 CIPN would be 50% without prophylaxis and 20% with GJG prophylaxis, and assuming an 80% completion rate of four paclitaxel courses, the required sample size is 66 patients (1-β: 0.75, α: 0.1). The secondary endpoint includes time to the onset of CIPN G2, incidence rate and severity of CIPN at the end of each course, relative dose intensity of paclitaxel, adverse events other than CIPN. Enrollment began in 2022, and will be complete by 2025. Clinical trial information: 061210047.