title: A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.
abstract: The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.
authors.affiliation: Department of Haematology, Royal Victoria Infirmary, Newcastle Upon Tyne, UK. dept.haem@newcastle.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.forename: P
authors.initials: P
authors.lastname: Taylor
authors.forename: G M
authors.initials: GM
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Marcus
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Chu
authors.forename: T J
authors.initials: TJ
authors.lastname: Littlewood
authors.forename: A
authors.initials: A
authors.lastname: Duncombe
authors.forename: M
authors.initials: M
authors.lastname: Hutchinson
authors.forename: A B
authors.initials: AB
authors.lastname: Mehta
authors.forename: S A
authors.initials: SA
authors.lastname: Johnson
authors.forename: P
authors.initials: P
authors.lastname: Carey
authors.forename: M J
authors.initials: MJ
authors.lastname: MacKie
authors.forename: P S
authors.initials: PS
authors.lastname: Ganly
authors.forename: G E
authors.initials: GE
authors.lastname: Turner
authors.forename: M
authors.initials: M
authors.lastname: Deane
authors.forename: S
authors.initials: S
authors.lastname: Schey
authors.forename: J
authors.initials: J
authors.lastname: Brookes
authors.forename: S M
authors.initials: SM
authors.lastname: Tollerfield
authors.forename: M P
authors.initials: MP
authors.lastname: Wilson
mesh_terms: D000208:Acute Disease; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine