gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

First line therapy with Fludarabine (F) versus Chlorambucil (CLB) in elderly patients (PTS) with advanced CLL: results of a multicentre phase III study (CLL5 protocol) of the German CLL Study Group (GCLLSG)

Meeting Abstract

  • corresponding author presenting/speaker Barbara Eichhorst - Universitätsklinikum, Köln, Deutschland
  • Raymonde Busch - Universitätsklinikum Technische Universität, München
  • Martina Stauch - DCLLSG
  • Manuela Bergmann - DCLLSG
  • Matthias Ritgen - DCLLSG
  • Nicole Kranzhöfer - DCLLSG
  • Robert Rohrberg - DCLLSG
  • Ulrike Söling - DCLLSG
  • Oswald Burkhard - DCLLSG
  • Berthold Emmerich - DCLLSG
  • Günter Brittinger - DCLLSG
  • Michael Hallek - Universitätsklinikum, Köln

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP102

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Veröffentlicht: 20. März 2006

© 2006 Eichhorst et al.
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Introduction: Fludarabine (F) based regimen have become the standard first line therapy in younger CLL patients (pts), but chlorambucil (Clb) is still frequently used in elderly pts. The GCLLSG initiated the CLL5 protocol, a phase III study without cross-over, to evaluate the effect of F versus (vs.) Clb as well as the quality of life (QOL) in first line therapy of elderly pts with advanced CLL.

Patients: From July 1999 to September 2003 206 pts with an age between 65 and 79 years were enrolled. Pts were randomized to receive either F 25mg/m² i.v. d1-5 q 28 days for 6 courses (101 pts) or Clb 0,4mg/kg ideal bodyweight (BW) d1 and d15 for 12 months (105 pts). Anti-infective prophylaxis and growth factors were not given routinely. The EORTC QoL-C30 questionnaire was sent to the pts at inclusion into the protocol and after 6, 12 and 24 months.

Results: 15 pts had to be excluded due to a protocol violation. 161 pts (77 pts with F and 84 pts Clb) with a median age of 70.3 years were evaluable for response. 15% of the pts were in Binet stage A, 44% in stage B, and 37% in stage C. No data were available in 4%. A mean of 4.9 courses of F and 6.5 months of Clb treatment was administered. The overall response rate (ORR) and complete remission rate (CRR) were significantly higher with F therapy than with Clb (ORR 86% vs. 57%, p<0.001; CRR 8% vs. 1%; p=0.04). After a median observation time of 24 months the median progression-free survival was significantly longer in F-treated pts (22 months) compared to Clb-treated pts (18 months; p=0.02). So far there is no significant difference in the OS between the two arms. 173 pts were available for toxicities. Severe myelotoxicity and in particular severe leukocytopenia was more common with F therapy (42% vs. 22%, p=0.004 and 27% vs. 0%, p<0.001). Surprisingly, there was no significant difference in the rate and severity of infection between the two arms (F vs. Clb: 22% vs. 25% and 7% vs. 3%). Four therapy related deaths due to severe infection were reported, three of them occurred during treatment with F. Within 30 months after study entry the incidence of Richter’s transformation (6% versus 0%; p=0.03) was significantly higher in the F arm. A preliminary analysis of QOL showed a significantly improved global health status in the F arm compared to Clb (plus 19 points on global health scale vs. minus 11 points; p = 0,022). Physical function was significantly improved in pts who had responded. In all other functional scales there was no significant difference between the two arms.

Conclusion: In conclusion, the results confirm findings in younger CLL patients of F being superior to Clb in inducing remissions and causing longer-lasting remissions in patients older than 65 years. Though F is well tolerated in elderly pts with adequate physical fitness and improves the global health status it induces a higher incidence of Richter’s transformation.