First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

Barbara F. Eichhorst, Raymonde Busch, Stephan Stilgenbauer, Martina Stauch, Manuela A. Bergmann, Matthias Ritgen, Nicole Kranzhöfer, Robert Rohrberg, Ulrike Söling, Oswald Burkhard, Anne Westermann, Valentin Goede, Carmen D. Schweighofer, Kirsten Fischer, Anna-Maria Fink, Clemens M. Wendtner, Günter Brittinger, Hartmut Döhner, Bertold Emmerich, Michael Hallek and the German CLL Study Group (GCLLSG)


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/m2 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 under identifier ISRCTN 36294212.

  • Submitted February 20, 2009.
  • Accepted June 27, 2009.
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