title: Efficacy and safety of oral fludarabine phosphate in previously untreated patients with chronic lymphocytic leukemia.
abstract: OBJECTIVE
  A prospective, multicenter, open-label, phase II clinical trial to assess oral fludarabine phosphate treatment in terms of safety, efficacy, and quality of life. Reference to a historical group of patients treated with the intravenous (IV) formulation allowed the two formulations to be compared.
  
  
  METHODS
  Patients with previously untreated B-cell chronic lymphocytic leukemia received 10-mg tablets of fludarabine phosphate to a dose of 40 mg/m(2)/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles. Efficacy was assessed using International Workshop on Chronic Lymphocytic Leukemia and National Cancer Institute criteria for response. Safety monitoring included WHO toxicity grading for adverse events. Quality of life was also assessed.
  
  
  RESULTS
  Eighty-one patients received treatment. According to International Workshop on Chronic Lymphocytic Leukemia criteria, the overall response rate was 71.6% (complete remission, 37.0%; partial remission, 34.6%). The response rate using National Cancer Institute criteria was 80.2% (complete remission, 12.3%; partial remission, 67.9%). Median time to progression was 841 days (range, 28 to 1,146 days). The most frequently reported grade 3/4 toxicity was myelosuppression. WHO grade 3/4 hematological toxicities included granulocytopenia (32.1%), anemia (9.9%), and thrombocytopenia (4.9%). Gastrointestinal toxicity was more common with the oral formulation than with IV fludarabine phosphate, but was generally mild to moderate and did not require treatment. Statistically significant improvements in mean emotional and insomnia quality-of-life scores were seen after treatment.
  
  
  CONCLUSIONS
  This study demonstrates that oral fludarabine phosphate is clinically effective and generally well tolerated by patients with previously untreated B-cell chronic lymphocytic leukemia. Oral fludarabine phosphate has a similar clinical efficacy and safety profile to the IV formulation. Oral fludarabine phosphate does not adversely affect quality of life and may improve emotional and insomnia scores.
authors.affiliation: CHU, Montpellier, France. jf-rossi@chu-montpellier.fr
authors.forename: J-F
authors.initials: JF
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: van Hoof
authors.forename: K
authors.initials: K
authors.lastname: de Boeck
authors.forename: S A
authors.initials: SA
authors.lastname: Johnson
authors.forename: D
authors.initials: D
authors.lastname: Bron
authors.forename: C
authors.initials: C
authors.lastname: Foussard
authors.forename: T A
authors.initials: TA
authors.lastname: Lister
authors.forename: C
authors.initials: C
authors.lastname: Berthou
authors.forename: M H H
authors.initials: MH
authors.lastname: Kramer
authors.forename: T J
authors.initials: TJ
authors.lastname: Littlewood
authors.forename: R E
authors.initials: RE
authors.lastname: Marcus
authors.forename: E
authors.initials: E
authors.lastname: Deconinck
authors.forename: M
authors.initials: M
authors.lastname: Montillo
authors.forename: O
authors.initials: O
authors.lastname: Guibon
authors.forename: S M
authors.initials: SM
authors.lastname: Tollerfield
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012074:Remission Induction; D012189:Retrospective Studies; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate