title: Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial.
abstract: A French and Belgian multicenter phase 3 trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia. Of 178 patients enrolled in the study, 165 were randomly assigned to receive 6 courses of oral fludarabine and cyclophosphamide (FC) in combination with rituximab (FCR; 375 mg/m(2) in cycle one, 500 mg/m(2) in all subsequent cycles) or alemtuzumab (FCCam; 30 mg subcutaneously injected on cycle days 1-3); each cycle was 28 days. Recruitment was halted prematurely because of excess toxicity; 8 patients died in the FCCam group, 3 from lymphoma and 5 from in-fection. Overall response rates were 91% with FCR and 90% with FCCam (P = .79). Complete remission rates were 33.75% with FCR and 19.2% with FCCam (P = .04). Three-year progression-free survival was 82.6% with FCR and 72.5% with FCCam (P = .21). Three-year overall survival was similar between the 2 arms at 90.1% in the FCR arm and 86.4% in the FCCam arm (P = .27). These results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use. This study is registered with www.clinicaltrials.gov as number NCT00564512.
authors.affiliation: Service d'Hématologie, Centre Henri Becquerel, Rouen, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Lepretre
authors.forename: Therese
authors.initials: T
authors.lastname: Aurran
authors.forename: Beatrice
authors.initials: B
authors.lastname: Mahé
authors.forename: Bruno
authors.initials: B
authors.lastname: Cazin
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.forename: Herve
authors.initials: H
authors.lastname: Maisonneuve
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.forename: Alain
authors.initials: A
authors.lastname: Delmer
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.forename: Bernadette
authors.initials: B
authors.lastname: Corront
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Roselyne
authors.initials: R
authors.lastname: Delépine
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vaudaux
authors.forename: Eric
authors.initials: E
authors.lastname: Van Den Neste
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Béné
authors.forename: Remi
authors.initials: R
authors.lastname: Letestu
authors.forename: Florence
authors.initials: F
authors.lastname: Cymbalista
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D015996:Survival Rate; D013997:Time Factors; 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