title: Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study.
abstract: BACKGROUND
  Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG's potential for reducing peripheral neuropathy in patients with colorectal cancer.
  
  
  METHODS
  Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
  
  
  RESULTS
  An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007).
  
  
  CONCLUSIONS
  Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.
authors: Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan, okieiji@surg2.med.kyushu-u.ac.jp.
authors: Eiji
authors: E
authors: Oki
authors: Yasunori
authors: Y
authors: Emi
authors: Hiroshi
authors: H
authors: Kojima
authors: Jun
authors: J
authors: Higashijima
authors: Takeshi
authors: T
authors: Kato
authors: Yasuhiro
authors: Y
authors: Miyake
authors: Masanori
authors: M
authors: Kon
authors: Yutaka
authors: Y
authors: Ogata
authors: Kenichi
authors: K
authors: Takahashi
authors: Hideyuki
authors: H
authors: Ishida
authors: Hiroshi
authors: H
authors: Saeki
authors: Yoshihisa
authors: Y
authors: Sakaguchi
authors: Takeharu
authors: T
authors: Yamanaka
authors: Toru
authors: T
authors: Kono
authors: Naohiro
authors: N
authors: Tomita
authors: Hideo
authors: H
authors: Baba
authors: Ken
authors: K
authors: Shirabe
authors: Yoshihiro
authors: Y
authors: Kakeji
authors: Yoshihiko
authors: Y
authors: Maehara
mesh_terms: D000368:Aged; 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; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D004365:Drugs, Chinese Herbal; D009944:Organoplatinum Compounds; C119642:gosha-jinki-gan; D002955:Leucovorin; D005472:Fluorouracil
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