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3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT
Southampton Univ Hosp NHS Fdn Trust, Southampton, Hants, England.
Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
Univ Oxford, Dept Oncol, Oxford, England.
Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
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2019 (English)In: Health Technology Assessment, ISSN 1366-5278, E-ISSN 2046-4924, Vol. 23, no 64, p. 1-88Article in journal (Refereed) Published
Abstract [en]

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.

Objective: 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 outcomes 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 pound per quality-adjusted life-year per patient.

Result: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. 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. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade >= 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to >= 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost 4881 pound less over the 8-year analysis period, with an incremental net monetary benefit of 7246 pound per patient.

Conclusions: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease.

Place, publisher, year, edition, pages
NIHR JOURNALS LIBRARY , 2019. Vol. 23, no 64, p. 1-88
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-402658DOI: 10.3310/hta23640ISI: 000503987000001PubMedID: 31852579OAI: oai:DiVA.org:uu-402658DiVA, id: diva2:1387026
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Swedish Cancer SocietyAvailable from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved

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