title: Progress in the treatment of chronic lymphocytic leukemia: results of the German CLL8 trial.
abstract: Until now, no approach that is able to improve overall survival of chronic lymphocytic leukemia (CLL) patients has been available. In the German CLL Study Group (GCLLSG) CLL8 trial, treatment-naive, physically fit patients (aged 30-81 years) with CD20(+) CLL were randomly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days of each 28-day treatment course with or without rituximab (375 mg/m(2) on day 0 of first course and 500 mg/m(2) on day 1 of second to sixth courses). The two groups were well balanced with respect to baseline characteristics. The study was stopped at the preplanned interim analysis owing to an advantage in the median progression-free survival in the chemoimmunotherapy arm (51.8 vs 32.8 months; hazard ratio: 0.56; 95% CI: 0.46-0.69; p < 0.0001). Furthermore, at 3 years after randomization, 87% of patients in the chemoimmunotherapy group were alive compared with 83% in the chemotherapy group (hazard ratio: 0.67; 95% CI: 0.48-0.92; p = 0.01). In terms of toxicity, chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia (p < 0.0001). There were eight (2%) treatment related-deaths in the chemoimmunotherapy arm compared with ten (3%) in the chemotherapy arm. The CLL8 trial has demonstrated that an association of rituximab, fludarabine and cyclophosphamide is effective in prolonging progression-free survival and overall survival of patients with symptomatic CLL, therefore establishing the new standard of treatment for physically fit patients.
authors.affiliation: Department of Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Viale Pio X, 88100 Catanzaro, Italy. smolica@libero.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008875:Middle Aged; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine