title: Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia.
abstract: This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab (R) and fludarabine (F) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia (CLL). The rationale for using R + F includes single-agent efficacy of both drugs, in vitro synergism of R and F, and no apparent overlapping toxicity. Of 31 eligible patients with B-CLL enrolled, 20 were previously untreated and 11 relapsed. Treatment consisted of fludarabine administered at standard doses (25 mg/m(2)/d; days 1-5, 29-33, 57-61, and 85-89) and rituximab (375 mg/m(2)/d) given on days 57, 85, 113, and 151. Side effects such as fever, chills, and exanthema were generally mild (National Cancer Institute Common Toxicity Criteria [NCI-CTC] grade 1/2 in 48% and grade 3 and/or 4 in 3% of patients). Fever and chills were mainly associated with the first rituximab infusion. Hematologic toxicity included neutropenia (grade 1 and/or 2 in 26%, grade 3 and/or 4 in 42%) and thrombocytopenia (grade 1 and/or 2 in 19%, grade 3 and/or 4 in 9%). One patient died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine. There were a total of 32 infections in 16 patients, none of which was fatal. The overall response rate (complete remission [CR] and partial remission [PR]) was 87% (27 of 31 evaluable patients). In 20 previously untreated patients, 17 (85%) responded. Ten of 31 patients achieved CR (5 of 20 untreated; 5 of 11 pretreated; 9 of 21 Binet stage B, 1 of 10 Binet stage C). The median duration of response was 75 weeks. We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL.
authors.affiliation: Clinic I of Internal Medicine, University of Cologne, Cologne 50924, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Saskia Karina
authors.initials: SK
authors.lastname: Klein
authors.forename: Ute
authors.initials: U
authors.lastname: Rehwald
authors.forename: Marcel
authors.initials: M
authors.lastname: Reiser
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Wolfgang-Ulrich
authors.initials: WU
authors.lastname: Knauf
authors.forename: Walter-Erich
authors.initials: WE
authors.lastname: Aulitzky
authors.forename: Manfred
authors.initials: M
authors.lastname: Hensel
authors.forename: Michael
authors.initials: M
authors.lastname: Herold
authors.forename: Dieter
authors.initials: D
authors.lastname: Huhn
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Volker
authors.initials: V
authors.lastname: Diehl
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D023341:Chills / Q000139:chemically induced; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007167:Immunotherapy; D007239:Infections / Q000453:epidemiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine