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Acute Leukemias

The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome

Leukemia volume 25, pages 1122–1127 (2011)Cite this article

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Abstract

Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC+ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20 mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1–5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.

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Acknowledgements

We thank the staff of the Birmingham Clinical Trials Unit, Cancer Research UK for research funding, Cephalon for the provision of Arsenic Trioxide and the investigators who participated in the trial: Aalborg Hospital: Dr Mette Skov Holm; Aberdeen Royal Infirmary: Dr DJ Culligan; Addenbrooke′s Hospital: Dr C Crawley, Dr J Craig; Barnet General Hospital: Dr M Treacy; Belfast City Hospital: Dr F Jones, Dr Mary Frances McMullin, Dr RJG Cuthbert; Birmingham Heartlands Hospital: Prof DW Milligan, Dr R Lovell; Blackpool Victoria Hospital: Dr PA Cahalin, Dr PR Kelsey; Borders General Hospital: Dr J Tucker; Bristol Haematology & Oncology Centre: Dr R Evely; Christie Hospital: Dr M Dennis; Colchester General Hospital: Dr G Campbell, Dr Ti Maboreke; Countess Of Chester Hospital: Dr S Tueger; Crosshouse Hospital: Dr P Maclean; Falkirk And District Royal Infirmary: Dr RF Neilson; Gartnavel General Hospital: Dr M Drummond, Dr P McKay; Gloucestershire Royal Hospital: Dr J Ropner; Hereford County Hospital: Dr LG Robinson; Hillingdon Hospital: Dr K Patel; Hull Royal Infirmary: Dr S Ali; James Paget Hospital: Dr S Sadullah; Kent & Canterbury Hospital: Dr CFE Pocock, Dr K Saied, Dr V Ratnayake; King George Hospital: Dr I Grant; Leicester Royal Infirmary: Dr AE Hunter; Lincoln County Hospital: Dr K Saravanamuttu; Medway Maritime Hospital: Dr A Eden, Dr M Aldouri, Dr VE Andrews; Monklands Hospital: Dr JA Murphy; Ninewells Hospital: Dr K Gelly; Norfolk & Norwich University Hospital: Dr M Lawes; Northwick Park Hospital: Dr L Yung; Nottingham University Hospitals NHS Trust—City Hospital Campus: Dr E Das-Gupta, Dr J L Byrne, Professor NH Russell; Pilgrim Hospital: Dr V Tringham; Pinderfields General Hospital: Dr J Ashcroft, Dr P Moreton; Pontefract General Infirmary: Dr D Wright; Poole General Hospital: Dr AJ Bell; Queen Alexandra Hospital: Dr M Ganczakowski, Dr R Corser, Dr T Cranfield; Queen Elizabeth Hospital (Kings Lynn): Dr N Curtin; Queen′s Hospital, Romford: Dr I Grant; Rigshospitalet University Hospital: Dr J Jurlander, Dr L Kjeldsen; Royal Bournemouth General Hospital: Dr J Chacko; Royal Cornwall Hospital (Treliske): Dr J Blundell; Royal Free Hospital: Dr P Kottaridis; Royal United Hospital Bath: Dr C Knechtli, Dr S Wexler; Sandwell General Hospital: Dr F Wandroo, Dr J Gillson; Scunthorpe General Hospital: Dr S Jalihal; Singleton Hospital: Dr H Sati; Southampton General Hospital: Dr D Richardson; Southport & Formby District General Hospital: Dr D O′Brien; St Bartholomew′s Hospital: Dr H Oakervee; St Helier Hospital: Dr J Mercieca, Dr M Clarke, Dr S Knowles; Stoke Mandeville Hospital: Dr AM O′Hea, Dr H Eagleton; The Alexandra Hospital: Dr T Skibbe; The Great Western Hospital: Dr A Sternberg; The James Cook University Hospital: Dr A Wood, Dr C Millar; The Royal Bolton Hospital: Dr J Jip; The Royal Oldham Hospital: Dr A Allameddine, Dr V Sen; Trafford General Hospital: Dr P Carrington; University College Hospital: Dr A Khwaja, Dr K Yong; University Hospital Aintree: Dr R Salim, Dr W Sadik; University Hospital Coventry (Walsgrave): Dr B Harrison, Dr M Narayanan; University Hospital Of North Tees: Dr P Mounter; University Hospital Of Wales: Dr C Rowntree, Dr J Kell, Dr S Knapper; Victoria Hospital: Dr K Davidson, Dr S Rogers; West Middlesex University Hospital: Dr M Sekhar, Dr M Al-Obaidi; Western General Hospital: Dr PRE Johnson; Whiston Hospital: Dr Toby Nicholson; Worcestershire Royal Hospital: Dr N Pemberton, Dr S Shafeek; Wycombe General Hospital: Dr R Aitchison; Ysbyty Glan Clwyd: Dr C Hoyle, Dr E Heartin, Dr MJ Goodrick; Ysbyty Gwynedd : Dr DR Edwards, Dr J Seale.

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Authors and Affiliations

  1. Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, UK

    A K Burnett & R K Hills

  2. Department of Haematology, Leicester Royal Infirmary, Infirmary Square, Leicester, UK

    A Hunter

  3. Department of Haematology, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK

    D Milligan

  4. Department of Haematology, University Hospital of Wales, Heath Park, Cardiff, UK

    J Kell

  5. Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, UK

    K Wheatley

  6. Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, UK

    J Yin

  7. Cancer Research Centre, Queen′s University, Belfast City Hospital, Lisburn Road, Belfast, UK

    M-F McMullin

  8. Department of Haematology, Blackpool Victoria Hospital, Whinney Heys Rd, Blackpool, Lancashire, UK

    P Cahalin

  9. Department of Haematology, Addenbrooke's Hospital, Hills Road, Cambridge, UK

    J Craig

  10. Department of Haematology, Leeds General Infirmary, Gt. George Street, Leeds, UK

    D Bowen

  11. Department of Haematology, Nottingham City Hospital, Hucknall Road, Nottingham, UK

    N Russell

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  1. A K Burnett
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Correspondence to A K Burnett.

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Burnett, A., Hills, R., Hunter, A. et al. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome. Leukemia 25, 1122–1127 (2011). https://doi.org/10.1038/leu.2011.59

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