Abstract

Purine nucleoside analogues, cladribine(2-CdA) and fludarabine (FA), especially combined with cyclophosphamide (CY) are potent cytotoxic drugs for the treatment of chronic lymphocytic leukemia (CLL). In this randomized study we aimed to establish whether combination of 2-CdA plus CY (CC) with FA plus (FC) provide similar benefit to previously untreated patients with CLL. The trial was started in January 2004 and the recruitment was ended in May 2007. The study primary endpoints were overall response (OR) and complete response (CR). The secondary endpoints included progression free survival (PFS), overall survival (OS), minimal residual disease negativity (MRD/-/) and treatment related toxicity. Eligible patients were randomly assigned to receive 6 courses of either 2-CdA 0.12 mg/kg/d i.v. + CY 250 mg/m2/d i.v. or FA 25 mg/m2/d i.v. + CY 250 mg/m2/d, both combinations for 3 consecutive days. The treatment response and toxicity were evaluated according to NCI-WG guidelines. MRD was evaluated in patients with CR using four-color flow cytometry assay.

There were no significant difference in the rates of OR, CR, MRD negativity, grade 3/4 neutropenia, thrombocytopenia and infections. PFS and OS were also similar in both groups. In conclusion, CC and FC regimens are similarly active and toxic in previously untreated CLL, however trend of longer OS in CC group is observed.

Characteristic CC arm FC arm P value 
Pts enrolled 212 211 
Pts evaluated 184 187 
No of courses (median, range) 6 (2–6) 5 (2–6) 0.56 
OR (%) 163 (88.6) 159 (85.0) 0.31 
CR (%) 86 (46.7) 91 (48.7) 0.43 
MRD/–/ (%) 33 (68.8) 44 (72.1) 0.70 
PFS (median, years) 2.195 2.361 0.86 
Thrombocytopania gr 3/4 (%) 23 (12.6) 22 (11.6) 0.77 
Neutropenia gr 3/4 (%) 39 (21.4) 43 (22.8) 0.76 
Infection gr 3/4 (%) 53 (29.1) 54 (28.6) 0.91 
OS (median, years) 4.066 2.531 0.10 
Death (%) 37 (20.2) 53 (27.9) 
Characteristic CC arm FC arm P value 
Pts enrolled 212 211 
Pts evaluated 184 187 
No of courses (median, range) 6 (2–6) 5 (2–6) 0.56 
OR (%) 163 (88.6) 159 (85.0) 0.31 
CR (%) 86 (46.7) 91 (48.7) 0.43 
MRD/–/ (%) 33 (68.8) 44 (72.1) 0.70 
PFS (median, years) 2.195 2.361 0.86 
Thrombocytopania gr 3/4 (%) 23 (12.6) 22 (11.6) 0.77 
Neutropenia gr 3/4 (%) 39 (21.4) 43 (22.8) 0.76 
Infection gr 3/4 (%) 53 (29.1) 54 (28.6) 0.91 
OS (median, years) 4.066 2.531 0.10 
Death (%) 37 (20.2) 53 (27.9) 

Supported by grant LPO 5 BO1828 from Ministry of Science, Warsaw, Poland.

Disclosures: No relevant conflicts of interest to declare.

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