Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients

To comparatively assess first-line treatment with fludarabine and 2 anthrac ycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxoru bicin), in advanced stages of chronic lymphocytic leukemia (CLL), previousl y untreated patients with stage B or C CLL were randomly allocated to recei ve 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment res ponse, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (65 1 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FA MP; 71.1%; P <.0001 for each), including lower clinical remission rates (CA P, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P=.003). By contrast, median survival t ime did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of inf ections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compare d to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P=.003) and hair loss (P <.0001). For patien ts with stage B and C CLL first-line fludarabine and ChOP regimens both pro vided similar overall survival and close response rates, and better results than CAR However, there was an increase in clinical remission rate and a t rend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL. (C) 2001 by The American Society of Hematology.