Background: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard
adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is
associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy.
Objectives: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal
cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations.
Design: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial.
Setting: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern
Ireland), Denmark, Spain, Sweden, Australia and New Zealand.
Participants: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III
adenocarcinoma of the colon or rectum.
Interventions: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and
capecitabine, randomised to be administered over 3 or 6 months.
Main outcome measures: The primary outcome was disease-free survival. Overall survival, adverse
events, neuropathy and health-related quality of life were also assessed. The main cost categories were
chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost
comparisons and quality-adjusted life-year gains between the options and was reported as net monetary
benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient.
Results: The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the
6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95%
confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for
3-month adjuvant chemotherapy.
