Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial

Ann Oncol. 2021 Jan;32(1):77-84. doi: 10.1016/j.annonc.2020.10.480. Epub 2020 Oct 26.


Background: Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy.

Patients and methods: From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety.

Results: Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001).

Conclusions: Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option.

Clinical trial information: UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.

Keywords: adjuvant chemotherapy; high-risk stage II colon cancer; oxaliplatin; treatment duration.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Capecitabine / adverse effects
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / pathology
  • Disease-Free Survival
  • Fluorouracil / adverse effects
  • Humans
  • Japan
  • Leucovorin / adverse effects
  • Neoplasm Staging
  • Organoplatinum Compounds* / adverse effects
  • Oxaliplatin / adverse effects
  • Prospective Studies


  • Organoplatinum Compounds
  • Oxaliplatin
  • Capecitabine
  • Leucovorin
  • Fluorouracil