title: Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double‑blind, placebo‑controlled trial of goshajinkigan to prevent oxaliplatin‑induced neuropathy.
abstract: OBJECTIVE
  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.
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Munemoto
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takemoto
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; D009944:Organoplatinum Compounds; C119642:gosha-jinki-gan; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil