title: Dose-reduced fludarabine, cyclophosphamide and rituximab is well tolerated in older patients with chronic lymphocytic leukemia and has preserved therapeutic efficacy.
abstract: Despite its efficacy in prospective trials, full dose fludarabine, cyclophosphamide and rituximab (FCR) may be too toxic for elderly patients with chronic lymphocytic leukemia (CLL) in clinical practice. We retrospectively reviewed the impact of dose reductions in FCR therapy on the outcomes of 42 consecutive patients aged 65-87 (median 72) years. Despite a median cumulative fludarabine dose reduction of 50% from full dose, the objective response and complete response rates were 86% and 38% respectively (frontline 94%/59%; previously treated 80%/24%). Dose reductions of 25-75% were not significantly associated with inferior progression free survival compared to minimal reductions (≤25%) (p=0.49), and did not preclude deep responses, including six cases (14%) of minimal residual disease negativity. Although hematological and infectious toxicities were common, treatment limiting adverse effects were infrequent. Dose attenuated FCR appears to have preserved efficacy and may be a viable therapeutic option for elderly patients with CLL.
authors.affiliation: a Faculty of Medicine, Nursing and Health Sciences , Monash University , Clayton , Australia ;
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lew
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;|c University of Melbourne , Parkville , Australia ;
authors.forename: Chan Y
authors.initials: CY
authors.lastname: Cheah
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;|c University of Melbourne , Parkville , Australia ;
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Carney
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;|c University of Melbourne , Parkville , Australia ;
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;|c University of Melbourne , Parkville , Australia ;
authors.forename: Max
authors.initials: M
authors.lastname: Wolf
authors.affiliation: d Department of Hematology , St Vincent's Hospital , Fitzroy , Australia.
authors.forename: Ali
authors.initials: A
authors.lastname: Bazargan
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;
authors.forename: E Henry
authors.initials: EH
authors.lastname: Januszewicz
authors.affiliation: d Department of Hematology , St Vincent's Hospital , Fitzroy , Australia.
authors.forename: Robin
authors.initials: R
authors.lastname: Filshie
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;
authors.forename: David
authors.initials: D
authors.lastname: Westerman
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;|c University of Melbourne , Parkville , Australia ;
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: b Department of Hematology , Peter MacCallum Cancer Centre , East Melbourne , Australia ;|c University of Melbourne , Parkville , Australia ;
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D000069283:Rituximab / Q000008:administration & dosage; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Aged; antibodies; comorbidity; drug therapy; monoclonal; neoplasms; toxicity