title: Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: final results of JCOG0205.
abstract: BACKGROUND
  NSABP C-06 demonstrated the non-inferiority of oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) to weekly fluorouracil and folinate (5-FU/LV) with respect to disease-free survival (DFS) for stage II/III colon cancer. This is the first report of JCOG0205, which compared UFT/LV to standard 5-FU/levofolinate (l-LV) for stage III colorectal cancer patients who have undergone Japanese D2/D3 lymph node dissection.
  
  
  METHODS
  Patients were randomised to three courses of 5-FU/l-LV (5-FU 500 mg/m(2), l-LV 250 mg/m(2) on days 1, 8, 15, 22, 29, 36 every 8 weeks) or five courses of UFT/LV (UFT 300 mg m(-2)day(-1), LV 75 mg/day on days 1-28 every 5 weeks). The primary end-point was DFS. The sample size was 1100 determined with one-sided alpha of 0.05, power of 0.78 and non-inferiority margin of hazard ratio of 1.27. This trial is registered with UMIN-CTR (C000000193).
  
  
  RESULTS
  Between February 2003 and November 2006, 1,101 patients (1092 eligible patients) were randomised to 5-FU/l-LV (n=550) or UFT/LV (n=551). Median age: 61 years, colon/rectum: 67%/33%, number of positive nodes ⩽3/>3: 73%/27%, stage IIIa/IIIb: 75%/25%. The hazard ratio of DFS was 1.02 (91.3% confidence interval, 0.84-1.23), demonstrating the non-inferiority of UFT/LV (P=0.0236). Five-year overall survival (87.5%) was higher than that in NSABP C-06 (69.6%). Grade 3/4 toxicities were 8.4% neutropenia in 5-FU/l-LV and 8.7% alanine aminotransferase elevation in UFT/LV, respectively. The incidences of diarrhoea (9.6% versus 8.5%) and anorexia (4.0% versus 3.7%) were similar between the two arms. No treatment-related deaths were reported.
  
  
  CONCLUSIONS
  Adjuvant UFT/LV is non-inferior to standard 5-FU/l-LV with respect to DFS. UFT/LV should be an oral treatment option for patients with stage III colon cancer who have undergone Japanese D2/D3 lymph node dissection.
authors: National Cancer Center Hospital, Tokyo, Japan. Electronic address: yshimada@ncc.go.jp.
authors: Yasuhiro
authors: Y
authors: Shimada
authors: National Cancer Center Hospital, Tokyo, Japan.
authors: Tetsuya
authors: T
authors: Hamaguchi
authors: JCOG Data Center, National Cancer Center, Tokyo, Japan.
authors: Junki
authors: J
authors: Mizusawa
authors: National Cancer Center Hospital East, Chiba, Japan.
authors: Norio
authors: N
authors: Saito
authors: Aichi Cancer Center Hospital, Aichi, Japan.
authors: Yukihide
authors: Y
authors: Kanemitsu
authors: Chiba Cancer Center, Chiba, Japan.
authors: Nobuhiro
authors: N
authors: Takiguchi
authors: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Masayuki
authors: M
authors: Ohue
authors: Minoh City Hospital, Osaka, Japan.
authors: Takeshi
authors: T
authors: Kato
authors: Niigata Cancer Center Hospital, Niigata, Japan.
authors: Yasumasa
authors: Y
authors: Takii
authors: Yamagata Prefectural Central Hospital, Yamagata, Japan.
authors: Toshihiko
authors: T
authors: Sato
authors: Kansai Rosai Hospital, Hyogo, Japan.
authors: Naohiro
authors: N
authors: Tomita
authors: Shizuoka Cancer Center, Shizuoka, Japan.
authors: Shigeki
authors: S
authors: Yamaguchi
authors: Kanagawa Cancer Center, Kanagawa, Japan.
authors: Makoto
authors: M
authors: Akaike
authors: National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors: Hideyuki
authors: H
authors: Mishima
authors: National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
authors: Yoshiro
authors: Y
authors: Kubo
authors: JCOG Data Center, National Cancer Center, Tokyo, Japan.
authors: Kenichi
authors: K
authors: Nakamura
authors: JCOG Data Center, National Cancer Center, Tokyo, Japan.
authors: Haruhiko
authors: H
authors: Fukuda
authors: National Cancer Center Hospital, Tokyo, Japan.
authors: Yoshihiro
authors: Y
authors: Moriya
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D005641:Tegafur; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil
keywords: Adjuvant chemotherapy; Colon cancer; D2/D3 lymph node dissection; UFT/LV