3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT) : an international, randomised, phase 3, non-inferiority trial
Iveson, Timothy J. (University Hospital Southampton NHS Foundation Trust (Regne Unit))
Kerr, Rachel S. (Department of Oncology, University of Oxford, Oxford, UK)
Saunders, Mark P. (The Christie Hospital, Manchester, UK)
Cassidy, Jim (Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK)
Hollander, Niels Henrik (Westmead Hospital)
Tabernero, Josep (Vall d'Hebron Institut d'Oncologia)
Haydon, Andrew (Australasian Gastro-Intestinal Trials Group, Melbourne, VIC, Australia)
Glimelius, Bengt (IGP, University of Uppsala, Uppsala, Sweden)
Harkin, Andrea (Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK)
Allan, Karen (Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK)
McQueen, John (Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK)
Scudder, Claire (OCTO, University of Oxford, Department of Oncology, Oxford, UK)
Boyd, Kathleen A. (University of Glasgow. Institute of Health and Wellbeing)
Briggs, Andrew (Memorial Sloan-Kettering Cancer Centre)
Waterston, Ashita (Beatson West of Scotland Cancer Centre (Glasgow, Regne Unit))
Medley, Louise (Royal United Hospital, Bath, UK)
Wilson, Charles (Addenbrookes Hospital (Cambridge, Regne Unit))
Ellis, Richard (Royal Cornwall Hospital NHS Trust, Truro, UK)
Essapen, Sharadah (St Luke's Cancer Centre, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK)
Dhadda, Amandeep S. (Castle Hill Hospital)
Harrison, Mark (Mount Vernon Cancer Centre, Northwood, UK)
Falk, Stephen (Bristol Cancer Institute, Bristol, UK)
Raouf, Sherif (Barking Havering and Redbridge University Hospital NHS Trust, Barking, UK)
Rees, Charlotte (University Hospital Southampton NHS Foundation Trust (Regne Unit))
Olesen, Rene K. (Aarhus University Hospital (Aarhus, Dinamarca))
Propper, David (Barts Cancer Institute (BCI))
Bridgewater, John (UCL Cancer Institute, University College London, London UK)
Azzabi, Ashraf (Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK)
Farrugia, David (Gloucestershire Oncology Centre, Cheltenham General Hospital, Cheltenham, UK)
Webb, Andrew (Brighton and Sussex University Hospital Trust)
Cunningham, David (Royal Marsden Hospital (Regne Unit))
Hickish, Tamas (Poole Hospital, Bournemouth University, Bournemouth, UK)
Weaver, Andrew (Department of Oncology, Oxford University Hospitals Foundation Trust, Oxford, UK)
Gollins, Simon (North Wales Cancer Treatment Centre, Rhyl, UK)
Wasan, Harpreet S.. (Hammersmith Hospital (Londres))
Paul, James (Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Adenocarcinoma ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Capecitabine ; Chemotherapy ; Colorectal Neoplasms ; Disease-Free Survival ; Female ; Fluorouracil ; Humans ; Leucovorin ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; Oxaliplatin ; Peripheral Nervous System Diseases ; Quality of Life ; Survival Rate ; Time Factors
Published in:	The Lancet. Oncology, Vol. 19 (april 2018) , p. 562-578, ISSN 1474-5488

DOI: 10.1016/S1470-2045(18)30093-7
PMID: 29611518

17 p, 1.9 MB

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