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, German CLL Study Group (GCLLSG), U Elberskirch, K Posse, P Cramer, H M Schulz, C Treptow, S Stein, P Jenke, K Klein, C Ilgen, P Cremer, D Nagel, L Fischer von Weikersthal, S Müller, J Dani, H Fuss, M Scholz, A Krackhardt, S Srock, A Dietzmann, J Herrenberger, A Kirsch, H Lebahn, P Felderbauer, G Döring, U von Grünhagen, B Günther, T Göhler, H Becker, J Meiler, U Hauch, M Eckart, B Häcker, W Heit, U Dührsen, J Dürig, R Noppeney, T Reiber, H Lambertz, S Gerhardt, H R Schmitt, J Mittermüller, K Kohloch, S Schüttrumpf, H Eschenburg, R Rohrberg, M Schmidt, C Spohn, O Klein, G Schilling, G Schuch, H Dürck, J Wysk, G Kehrer, H Dietzfelbinger, I Rassmann, W Freier, A Eberle, H Pees, M Pfeifer, D Linck, M Bentz, M Schmier, M Kneba, D Böttcher, R Schoch, M Neugebauer, U Vehling-Kaiser, H Middeke, T Ulshöfer, J Schneider, J Bergmann, A Fuchs, E M Kalusche, J Lärmer, M Starck, M Hentrich, C Buske, M Dreyling, W Abenhardt, L Böhning, D Bosse, H Hitz, H D Schick, C Lerchenmüller, J Wehmeyer, P Schmidt, R Hoffmann, S Vartansever, G Hartwich, G Börg, H Balló, H F Hinrichs, B Ottembra, D Bachert, A Gerhardt, F Rothmann, A Steffen, S Wilhelm, M Baldus, A Rotter, J Preiss, G Jacobs, J Schimke, C Thiel, S Krauss, B Schmid, E Höring, M Clemens, I Kessler-Rieder, B Schubert, A Waladkhani, H P Laubenstein, M Söckler, J Diers, G Hopfinger, O Burkhard, B Reimann, R Schlag, M Sandmann, 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, German CLL Study Group (GCLLSG), U Elberskirch, K Posse, P Cramer, H M Schulz, C Treptow, S Stein, P Jenke, K Klein, C Ilgen, P Cremer, D Nagel, L Fischer von Weikersthal, S Müller, J Dani, H Fuss, M Scholz, A Krackhardt, S Srock, A Dietzmann, J Herrenberger, A Kirsch, H Lebahn, P Felderbauer, G Döring, U von Grünhagen, B Günther, T Göhler, H Becker, J Meiler, U Hauch, M Eckart, B Häcker, W Heit, U Dührsen, J Dürig, R Noppeney, T Reiber, H Lambertz, S Gerhardt, H R Schmitt, J Mittermüller, K Kohloch, S Schüttrumpf, H Eschenburg, R Rohrberg, M Schmidt, C Spohn, O Klein, G Schilling, G Schuch, H Dürck, J Wysk, G Kehrer, H Dietzfelbinger, I Rassmann, W Freier, A Eberle, H Pees, M Pfeifer, D Linck, M Bentz, M Schmier, M Kneba, D Böttcher, R Schoch, M Neugebauer, U Vehling-Kaiser, H Middeke, T Ulshöfer, J Schneider, J Bergmann, A Fuchs, E M Kalusche, J Lärmer, M Starck, M Hentrich, C Buske, M Dreyling, W Abenhardt, L Böhning, D Bosse, H Hitz, H D Schick, C Lerchenmüller, J Wehmeyer, P Schmidt, R Hoffmann, S Vartansever, G Hartwich, G Börg, H Balló, H F Hinrichs, B Ottembra, D Bachert, A Gerhardt, F Rothmann, A Steffen, S Wilhelm, M Baldus, A Rotter, J Preiss, G Jacobs, J Schimke, C Thiel, S Krauss, B Schmid, E Höring, M Clemens, I Kessler-Rieder, B Schubert, A Waladkhani, H P Laubenstein, M Söckler, J Diers, G Hopfinger, O Burkhard, B Reimann, R Schlag, M Sandmann
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.
Source: PubMed