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

• Published in: Blood Vol. 96; no. 8; pp. 2723 - 2729
• Main Authors: Robak, Tadeusz, Bloński, Jerzy Z., Kasznicki, Marek, Blasińska-Morawiec, Maria, Krykowski, Euzebiusz, Dmoszyńska, Anna, Mrugala-Śpiewak, Halina, Skotnicki, Aleksander B., Nowak, Wieslaw, Konopka, Lech, Ceglarek, Bernadeta, Maj, Stanislaw, Dwilewicz-Trojaczek, Jadwiga, Hellmann, Andrzej, Urasiński, Ignacy, Zdziarska, Barbara, Kotlarek-Haus, Sabina, Potoczek, Stanislaw, Grieb, Pawel
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2000; The Americain Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Chlorambucil - administration & dosage; Chlorambucil - adverse effects; Cladribine - administration & dosage; Cladribine - adverse effects; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Incidence; Infections - epidemiology; Infections - etiology; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Life Tables; Male; Medical sciences; Middle Aged; Neutropenia - chemically induced; Neutropenia - epidemiology; Pharmacology. Drug treatments; Poland - epidemiology; Prednisone - administration & dosage; Prednisone - adverse effects; Prospective Studies; Remission Induction; Survival Rate; Thrombocytopenia - chemically induced; Thrombocytopenia - epidemiology; Treatment Outcome; Poland; Antineoplastic agent; Human; Corticosteroid; Drug combination; Purine nucleoside; Multicenter study; Malignant hemopathy; Prednisone; Deoxyribonucleoside; Chlorambucil; Alkylating agent; Chemotherapy; Chronic; Chronic lymphocytic leukemia; Randomization; Treatment; Antimetabolic; Lymphoproliferative syndrome; Cladribine; Clinical trial; Comparative study
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.8.2723

The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chlorambucil (Chl) + P were compared in previously untreated patients with progressive 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/m2 per day for 5 consecutive days or Chl 12 mg/m2 per day and P 30 mg/m2 per day for 7 consecutive days. Three courses were administered at 28-day intervals or longer if myelosuppression developed. The therapy was finished if complete response (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 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%, respectively) (P = .001). Progression-free survival was significantly longer in the 2-CdA–treated group (P = .01), but event-free survival was not statistically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P = .001). Drug-induced neutropenia was more frequently observed during 2-CdA+P (23%) than Chl+P therapy (11%) (P = .02), but thrombocytopenia occurred with similar frequency in both groups (36% and 27%, respectively). 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 been similar in patients treated with 2-CdA (20%) and with Chl (17%). The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively).