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

Eur J Cancer. 2014 Sep;50(13):2231-40. doi: 10.1016/j.ejca.2014.05.025. Epub 2014 Jun 20.

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).

Findings: 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.

Interpretation: 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.

Keywords: Adjuvant chemotherapy; Colon cancer; D2/D3 lymph node dissection; UFT/LV.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Japan
  • Leucovorin / administration & dosage
  • Lymph Node Excision
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Tegafur / administration & dosage
  • Uracil / administration & dosage
  • Young Adult

Substances

  • Tegafur
  • Uracil
  • Leucovorin
  • Fluorouracil