학술논문
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
Document Type
article
Author
Timothy Iveson; Kathleen A Boyd; Rachel S Kerr; Jose Robles-Zurita; Mark P Saunders; Andrew H Briggs; Jim Cassidy; Niels Henrik Hollander; Josep Tabernero; Andrew Haydon; Bengt Glimelius; Andrea Harkin; Karen Allan; John McQueen; Sarah Pearson; Ashita Waterston; Louise Medley; Charles Wilson; Richard Ellis; Sharadah Essapen; Amandeep S Dhadda; Mark Harrison; Stephen Falk; Sherif Raouf; Charlotte Rees; Rene K Olesen; David Propper; John Bridgewater; Ashraf Azzabi; David Farrugia; Andrew Webb; David Cunningham; Tamas Hickish; Andrew Weaver; Simon Gollins; Harpreet Wasan; James Paul
Source
Health Technology Assessment, Vol 23, Iss 64 (2019)
Subject
Language
English
ISSN
1366-5278
2046-4924
2046-4924
Abstract
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: 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