A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment


  • See related Editorial on pages 000–000, this issue.

  • The following investigators entered patients in this trial: Aberdeen Royal Infirmary: Dr. D. J. Culligan and Dr. J. Tighe; Altnagelvin Area Hospital: Dr. M. F. Ryan; Arrowe Park Hospital: Dr. D. W. Galvani; Barnet General Hospital: Dr. A. Virchis; Belfast City Hospital: Dr. R. J. G. Cuthbert, Dr. M. F. McMullin, and Dr. T. C. M. Morris; Bradford Royal Infirmary: Dr. L. A. Parapia and Dr. A. T. Williams; Bristol Royal Infirmary: Dr. G. L. Scott and Dr. G. R. Standen; Broadgreen Hospital: Dr. P. Chu; Canterbury Health Laboratories: Dr. W. N. Patton; Central Middlesex Hospital: Dr. K. Ryan; Christchurch Hospital: Dr. R. L. Spearing; Christie Hospital: Dr. R. Chopra; City Hospital National Health Service (NHS) Trust: Dr. D. Bareford and Dr. J. G. Wright; Conquest Hospital: Dr. J. Beard; Craigavon Area Hospital: Dr. C. Humphrey; Crosshouse Hospital: Dr. J. G. Erskine and Dr. P. D. Micallef Eynaud; Derbyshire Royal Infirmary: Dr. D. C. Mitchell; Ealing Hospital: Dr. G. Abrahamson; Eastbourne District General: Dr. P. A. Gover; Falkirk District Royal Infirmary: Dr. A. D. J. Birch; Glan Clwyd Hospital: Dr. D. R. Edwards and Dr. D. I. Gozzard; Gloucestershire Royal Hospital: Dr. J. Ropner; Good Hope Hospital NHS Trust: Dr. M. A. Lumley; Guy's Hospital: Dr. R. Carr; Harrogate District Hospital: Dr. A. G. Bynoe and Dr. M. W. McEvoy; Hull Royal Infirmary: Dr. S. Ali; Ipswich Hospital: Dr. J. A. Ademokun; Kent and Canterbury Hospital: Dr. C. F. E. Pocock; Kingston Hospital NHS Trust: Dr. Z. Abboudi; Leeds General Infirmary: Prof. J. A. Child, Dr. D. R. Norfolk, and Dr. G. M. Smith; Leicester Royal Infirmary: Dr. C. S. Chapman, Dr. A. E. Hunter, Dr. D. B. J. Kennedy, and Dr. J. A. Snowden; Llandough Hospital NHS Trust: Dr. D. P. Bentley; Manchester Royal Infirmary: Prof. J. A. Liu Yin and Dr. G. S. Lucas; Monklands District General: Dr. G. Cook, Dr. J. A. Murphy, and Dr. W. Watson; Nevill Hall Hospital: Dr. G. T. M. Robinson; North Staffs Hospital Centre: Dr. R. C. Chasty and Dr. K. P. Schofield; Nottingham City Hospital: Dr. P. A. E. Jones and Prof. N. H. Russell; Oldchurch Hospital: Dr. A. Brownell; Pinderfields General Hospital: Dr. M. C. Galvin and Dr. P. Hillmen; Queen Alexandra Hospital: Dr. M. Ganczakowski; Queen Elizabeth Hospital: Dr. J. Keidan; Raigmore Hospital: Dr. P. Forsyth; Royal Berkshire Hospital: Dr. F. B. BritoBabapulle, Dr. H. Grech, and Dr. G. Morgenstern; Royal Bolton Hospital: Dr. J. Jip; Royal Chesterfield Hospital: Dr. R. Stewart; Royal Devon and Exeter Hospital: Dr. M. V. Joyner, Dr. R. Lee, and Dr. M. A. Pocock; Royal Free Hospital: Dr. A. B. Mehta; Royal Gwent Hospital: Dr. H. A. Jackson; Royal Liverpool University Hospital: Prof. R. E. Clark and Dr. A. R. Pettitt; Royal Surrey County Hospital: Dr. G. Robbins; Russells Hall Hospital: Dr. P. Harrison and Dr. J. Neilson; Salisbury District Hospital: Dr. J. O. Cullis; Sandwell General Hospital: Dr. S. I. Handa; Scunthorpe General Hospital: Dr. R. A. Ezekwesili; Singleton Hospital: Dr. S. Al-Ismail; Southampton University Hospital Trust: Dr. A. Duncombe and Dr. K. Orchard; Southern General Hospital: Dr. A. E. Morrison; St. Helier Hospital: Dr. J. Mercieca; St. James's University Hospital: Dr. D. L. Barnard and Dr. B. A. McVerry; Staffordshire General Hospital: Dr. P. Revell; Stoke Mandeville Hospital: Dr. A. Watson; Sundsvall Hospital: Dr. J. Wallvik; Torbay Hospital: Dr. F. Booth; University College Hospital: Dr. K. G. Patterson and Dr. K. Yong; University Hospital Aintree: Dr. W. Sadik; University Hospital Lewisham: Dr. N. Mir; University Hospital of Wales: Prof. A. K. Burnett, Dr. C. Poynton, and Dr. J. A. Whittaker; University Hospitals Coventry and Warwickshire: Dr. S. Basu, Dr. B. Harrison, and Dr. J. Mills; University of Ioannina: Prof. K. L. Bourantas; Victoria Infirmary: Dr. P. J. Tansey; Western General Hospital: Dr. J. M. Davies, Dr. P. R. E. Johnson, and Dr.A. C. Parker; Whipps Cross Hospital: Dr. C. DeSilva; Whiston Hospital: Dr. G. Satchi; Wycombe General Hospital: Dr. R. Aitchison; York Hospital: Dr. L. R. Bond and Dr. M. R. Howard; and Ysbyty Gwynedd: Dr. D. H. Parry.



The survival of older patients with acute myeloid leukemia has not improved. Few clinical trials have been available for older patients who are not considered fit for an intensive chemotherapy approach.


Between December 1998 and November 2003, as part of National Cancer Research Institute Acute Myeloid Leukemia 14 Trial, 217 patients, who were deemed unfit for intensive chemotherapy were randomized to receive low-dose cytarabine (Ara-C) (20 mg twice daily for 10 days) or hydroxyurea with or without all-trans retinoic acid (ATRA).


Low-dose ara-C produced a better remission rate (18% vs 1%; odds ratio [OR], 0.15; 95% confidence interval [95% CI], 0.06–0.37; P = .00006) and better overall survival (OR, 0.60; 95% CI, 0.44–0.81; P = .0009), which was accounted for by the achievement of complete remission (CR) (duration of CR: 80 weeks vs 10 weeks for patients with no CR). Patients who had adverse cytogenetics did not benefit. ATRA had no effect. Toxicity scores or supportive care requirements did not differ between the treatment arms.


Older, less fit patients have a poor outcome, and few trials have been conducted in this patient group. Low-dose ara-C treatment was superior to best supportive care and hydroxyurea because it had greater success in achieving CR, and it could represent standard care against which new treatments may be compared in this patient group. [See editorial on pages 000–000, this issue.] Cancer 2007 © 2007 American Cancer Society.