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 5-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chi 12 mg/m2 per day and P 30 mg/m(2) per day for 7 con secutive days. Three courses were administered at 28-day intervals or longe r if myelosuppression developed. The therapy was finished if complete respo nse (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 1 03 received Chl+P as a first-line treatment. CR and overall response rates were significantly higher in the patients treated with 2-CdA+P (47% and 87% , respectively) than in the patients treated with Chl+P (12% and 57%, respe ctively) (P =.001). Progression-free survival was significantly longer in t he 2-CdA-treated group (P =.01), but event-free survival was not statistica lly different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P =.001). Drug-induced neutropenia was more frequently observ ed during 2-CdA+P (23%) than Chl+P therapy (11%) (P =.02), but thrombocytop enia occurred with similar frequency in both groups (36% and 27%, respectiv ely). Infections were seen more frequently in the 2-CdA+P-treated group (56 %) than in the Chl+P-treated group (40%; P=.02). Death rates have so far be en similar in patients treated with 2-CdA (20%) and with Chi (17%), The pro bability of overall survival calculated from Kaplan-Meier curves at 24 mont hs was also similar for both groups (78% and 82%, respectively). (Blood. 20 00;96:2723-2729) (C) 2000 by The American Society of Hematology.