title: Fludarabine + prednisone +/- alpha-interferon followed or not by alpha-interferon maintenance therapy for previously untreated patients with chronic lymphocytic leukemia: long term results of a randomized study.
abstract: OBJECTIVE
  Fludarabine is an effective therapy for patients with chronic lymphocytic leukemia (CLL) and interferon-alpha (IFN-alpha) has been reported to have anti-leukemic activity in CLL patients. A randomized study was designed to evaluate whether the addition of IFN-alpha to a first-line treatment with fludarabine and prednisone could increase the response rate in patients with advanced CLL and whether IFN-alpha given as maintenance therapy could improve the duration of response.
  
  
  METHODS
  One hundred and thirty-three patients were randomized to receive fludarabine (25 mg/m2/i.v., days 9-13) and prednisone (20 mg/m2, days 1, 3, 5, 7 and 14 and 40 mg/m2, days 9-13) (arm A: 66 patients) or in addition to the same schedule, IFN-alpha (2 MUI/sc, days 1, 3, 5, 7, 9, 11, 13 and 15) (arm B: 67 patients). Seventy-eight patients responsive to therapy entered the post-remission phase of the study in which 41 patients were randomized to receive IFN-alpha (3 MUI three times a week) and 37 to clinical observation.
  
  
  RESULTS
  A similar response rate (complete responses + partial responses) was observed in the 2 arms: 86% for arm A and 84% for arm B (p = 0.4). A longer response duration was observed in patients who achieved a complete response (p = 0.001) and in patients who received maintenance therapy with IFN-alpha (p < 0.05). However, the quality of response was the only significant and independent factor influencing response duration (p < 0.01). No benefits in terms of infection-related mortality and morbidity could be ascribed to IFN-alpha administration.
  
  
  CONCLUSIONS
  In previously untreated CLL patients with advanced disease a high response rate is obtained from first-line fludarabine and prednisone and no benefit is derived from the addition of IFN-alpha to this regimen. The achievement of a good quality response to therapy was the only independent predictor of a prolonged response.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, via Benevento 6, 00161 Rome, Italy. mauro@bce.med.uniroma1.it
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Mauro
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Zinzani
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Maria Luce
authors.initials: ML
authors.lastname: Vegna
authors.forename: Vittorio
authors.initials: V
authors.lastname: Stefoni
authors.forename: Luciana
authors.initials: L
authors.lastname: Marin
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D016898:Interferon-alpha; D014740:Vidarabine; C024352:fludarabine; D011241:Prednisone