title: A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia.
abstract: The development of new treatments for older patients with acute myeloid leukaemia (AML) is an active area, but has met with limited success. Sapacitabine is a novel orally administered nucleoside analogue that has shown encouraging activity in unrandomised early-stage trials. We randomised 143 untreated patients with AML or with high-risk myelodysplastic syndrome (>10% marrow blasts) between sapacitibine and low-dose ara-C (LDAC) in our 'Pick a Winner' trial design. At the planned interim analysis there was no difference between LDAC and sapacitibine in terms of remission rate (CR/CRi, 27% vs 16% hazard ratio (HR) 1.98(0.90-4.39) P=0.09), relapse-free survival (10% vs 14% at 2 years, HR 0.73(0.33-1.61) P=0.4) or overall survival (OS; 12% vs 11% at 2 years, HR 1.24(0.86-1.78) P=0.2). Sapacitibine was well tolerated, apart from more grade 3/4 diarrhoea. On the basis of these findings sapacitibine did not show sufficient evidence of benefit over LDAC for the trial to be continued.
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
authors: A K
authors: AK
authors: Burnett
authors: Department of Haematology, Nottingham University Hospital NHS Trust, Nottingham, UK.
authors: N
authors: N
authors: Russell
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
authors: R K
authors: RK
authors: Hills
authors: Northwick Park Hospital, Harrow, UK.
authors: N
authors: N
authors: Panoskaltsis
authors: University College London Hospitals, 1st Floor Central, London, UK.
authors: A
authors: A
authors: Khwaja
authors: Queen's Hospital, Rom Valley Way, Romford, UK.
authors: C
authors: C
authors: Hemmaway
authors: Blackpool Victoria Hospital, Blackpool, UK.
authors: P
authors: P
authors: Cahalin
authors: Department of Haematology, Royal Liverpool University Hospital, Prescot St, Liverpool, UK.
authors: R E
authors: RE
authors: Clark
authors: Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK.
authors: D
authors: D
authors: Milligan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D001087:Arabinonucleosides; D003561:Cytarabine; D003596:Cytosine; C117959:sapacitabine