title: First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia.
abstract: Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m(2) for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with www.isrctn.org under identifier ISRCTN 36294212.
authors: Department I of Internal Medicine, Centre of Integrated Oncology Köln Bonn, University of Cologne, Cologne, Germany. barbara.eichhorst@uk-koeln.de
authors: Barbara F
authors: BF
authors: Eichhorst
authors: Raymonde
authors: R
authors: Busch
authors: Stephan
authors: S
authors: Stilgenbauer
authors: Martina
authors: M
authors: Stauch
authors: Manuela A
authors: MA
authors: Bergmann
authors: Matthias
authors: M
authors: Ritgen
authors: Nicole
authors: N
authors: Kranzhöfer
authors: Robert
authors: R
authors: Rohrberg
authors: Ulrike
authors: U
authors: Söling
authors: Oswald
authors: O
authors: Burkhard
authors: Anne
authors: A
authors: Westermann
authors: Valentin
authors: V
authors: Goede
authors: Carmen D
authors: CD
authors: Schweighofer
authors: Kirsten
authors: K
authors: Fischer
authors: Anna-Maria
authors: AM
authors: Fink
authors: Clemens M
authors: CM
authors: Wendtner
authors: Günter
authors: G
authors: Brittinger
authors: Hartmut
authors: H
authors: Döhner
authors: Bertold
authors: B
authors: Emmerich
authors: Michael
authors: M
authors: Hallek
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D002699:Chlorambucil / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D012074:Remission Induction; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D014740:Vidarabine; C024352:fludarabine