Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of goshajinkigan to prevent oxaliplatin-induced neuropathy

PURPOSE: Oxaliplatin-induced peripheral neurotoxicity (OPN) is frequent and potentially severe, but successful treatment of this condition is still an unmet clinical need. We aimed to determine whether treatment with goshajinkigan (TJ-107), a traditional Japanese medicine, is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with standard FOLFOX regimens. METHODS: In this phase 2, randomized, double-blind, placebo-controlled study, patients undergoing oxaliplatin-based chemotherapy were randomized to receive either oral TJ-107 (7.5 g) or matching placebo daily. The severity of OPN was assessed according to the Common Toxicity Criteria for Adverse Events at baseline, every 2 weeks until the 8th cycle, and every 4 weeks thereafter until the 26th week. The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy. RESULTS: Analyses were done by intention to treat. Eighty-nine patients were randomly assigned to receive either TJ-107 (n = 44) or placebo (n = 45) between May 2009 and March 2010. The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups, respectively (relative risk (RR), 0.76; 95 % CI, 0.47–1.21). The incidence of grade 3 OPN was 7 % (TJ-107) vs. 13 % (placebo) (0.51, 0.14–1.92). No concerns regarding toxicity emerged with TJ-107 treatment. CONCLUSIONS: TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy.