Adding Epirubicin to Fludarabine Boosts Response Rate but not Overall Survival

[Guest guest]

[2123] Fludarabine Versus Fludarabine Plus Epirubicin in the

Treatment of Chronic Lymphocytic Leukemia – Final Results of a

German Randomized Phase-III Study. Session Type: Poster Session 327-

II

Mathias J. Rummel, Stephan Stilgenbauer, Heinold Gamm, s Rost,

Doehner Hartmut, Dieter Hoelzer, Lothar Bergmann Hematology,

University Hospital, furt, Germany; Hematology, University

Hospital, Ulm, Germany; Hematology, University Hospital, Mainz,

Germany; Hematology, Staedtische Kliniken, Darmstadt, Germany

Based on promising results from our previous phase-II study

demonstrating an overall response rate (ORR) of 92% and a high rate

of complete remissions (CR) of 40% we initiated a multicenter

randomized phase-III study to compare efficacy and toxicity of the

combination fludarabine plus epirubicin (FluEpi) versus monotherapy

with fludarabine (Flu) as first-line therapy or therapy of first

relapse. In addition, cytogenetic aberrations were investigated in

all patients to evaluate, if special chromosomal abnormalities are

associated with prognosis and response to fludarabine. Treatment

schedule: Fludarabine 25 mg/qm day 1-5, epirubicin 25 mg/qm day 4+5

for a maximum of 6 cycles every four weeks.

Results: 150 patients (pts) are evaluable for response (77 pts with

Flu, 73 pts with FluEpi). Median age of the patients is 62 years.

All pts were in need of treatment with 86 pts being in stage Binet B

and 64 pts in Binet C. Cytogenetic aberrations were well balanced

between both groups. The ORR for the total group of 150 pts was 79%

with a CR-rate of 19%. The ORR for patients treated with FluEpi was

88% compared to patients treated with Flu monotherapy reaching an

ORR of 73%. This difference is statistical different with a p-value

of 0.0255. CR are different in favor for combined treatment modality

(29% CR for FluEpi vs 9% for Flu) with a significance level of

0.0029. Patients treated with FluEpi have a longer median duration

of progression free survival with 26 months in comparison to 20

months for patients treated with fludarabine alone (p=0.085). There

is a trend for a longer median overall survival time, which is 76

months for patients with FluEpi compared to the median survival time

of 63 months for the Flu monotherapy group, however this difference

is not statistical different (p=0.10).

The event free survival (EFS), which was defined as not achieving

any remission, progression/relpase of disease or death for any

cause, was superior for pts treated with FluEpi (30 months) in

comparison to the pts treated with Flu monotherapy (19 months) with

a significance level of 0.048.

Conclusions: The combination therapy of fludarabine plus epirubicin

achieves statistically higher response rates and a longer duration

of event free survival, however this does not translate in an

statistical significant overall survival benefit.