title: A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age.
abstract: Outcomes for older adults with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are generally poor, and new effective therapies are needed. We investigated oral clofarabine combined with low-dose cytarabine (LDAC) in patients aged 60 years and above with relapsed or refractory AML or high-risk MDS in a phase I/II trial. A 3 + 3 dose escalation of oral clofarabine was followed by a phase II expansion with the aim of obtaining a complete response (CR) rate ≥30%. We identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral clofarabine. A total of 35 patients, with a median age of 72 years, were treated. Of 26 patients enrolled at the MTD, 4 had treatment-related grade 3-4 non-haematological toxicities, but none died within 28 d. The observed CR rate and median survival were 34% [95% confidence interval (CI), 18-50%] and 6.8 months overall and 38% [95% CI, 19-57%] and 7.2 months at the MTD. The median disease-free survival was 7.4 months. Fifty-two percent (23/44) of cycles administered at the MTD were done without hospital admission. This combination of oral clofarabine and LDAC demonstrated efficacy with a CR rate of >30% and acceptable toxicity in older patients.
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Sarah A
authors: SA
authors: Buckley
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Raya
authors: R
authors: Mawad
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Ted A
authors: TA
authors: Gooley
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Pamela S
authors: PS
authors: Becker
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Vicky
authors: V
authors: Sandhu
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Paul
authors: P
authors: Hendrie
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Bart L
authors: BL
authors: Scott
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
authors: Brent L
authors: BL
authors: Wood
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Roland B
authors: RB
authors: Walter
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Kelly
authors: K
authors: Smith
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Carol
authors: C
authors: Dean
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Elihu H
authors: EH
authors: Estey
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors: John M
authors: JM
authors: Pagel
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001087:Arabinonucleosides / Q000008:administration & dosage; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine
keywords: acute myeloid leukaemia; clofarabine; elderly; myelodysplastic syndrome; phase I/II