Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial

The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chl orambucil (Chl) + P were compared in previously untreated patients with pro gressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized, multicenter prospective trial. Eligible patients were assigned to either 2 -CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chi 12 mg/m(2) per day and P 30 mg/m(2) per day for 7 c onsecutive days. Three courses were administered at 28-day intervals or lon ger if myelosuppression developed. The therapy was finished if complete res ponse (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 received ChI+P as a first-line treatment. OR and overall response rate s were significantly higher in the patients treated with 2-CdA+P (47% and 8 7%, respectively) than in the patients treated with ChI+P (12% and 57%, res pectively) (P = .001), Progression-free survival was significantly longer i n the 2-CdA-treated group (P = .01), but event-free survival was not statis tically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to ChI+P (P = .001). Drug-induced neutropenia was more frequently o bserved during 2-CdA+P (23%) than ChI+P therapy (11%) (P = .02), but thromb ocytopenia occurred with similar frequency in both groups (36% and 27%, res pectively). Infections were seen more frequently in the 2-CdA+P-treated gro up (56%) than in the ChI+P-treated group (40%; P = .02), Death rates have s o far been similar in patients treated with 2-CdA (20%) and with ChI (17%), The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively). (C ) 2000 by The American Society of Hematology.