title: The influence of increasing age on the deliverability and toxicity of fludarabine-based combination chemotherapy regimens in patients with indolent lymphoproliferative disorders.
abstract: BACKGROUND
  Fludarabine-based combination chemotherapy regimens are highly effective in the treatment of patients with indolent lymphoproliferative disorders. Despite the prevalence of such disorders in older patients, the effect of increasing age on the deliverability of these regimes has not been assessed.
  
  
  METHODS
  The authors analyzed the effect of increasing age on the deliverability and toxicity of 3 fludarabine-based regimens, all using fludarabine 25 mg/m2 per day for 3 days intravenously every 28 days, in 180 patients who were stratified into 2 age groups (age <60 years and age > or =60 years), with multivariate analysis to control for other differences between groups. The authors also explored the impact of age > or =70 years within the older cohort.
  
  
  RESULTS
  Older patients were more likely to experience an episode of nonsevere hematologic or infectious toxicity, but there was no difference in the rate of severe toxicity. Toxicity rates per cycle did not differ between age groups. The rates of neutropenia (absolute neutrophil count [ANC], < 1.0 x 10(9)/L) and severe neutropenia (ANC, 0.5 x 10(9)/L) were 22% and 13%, respectively, in older patients versus 20% and 11%, respectively, in younger patients (P > .1 for both). The rates of thrombocytopenia (platelet count, <100 x 10(9)/L) and severe thrombocytopenia (platelet count, <50 x 10(9)/L) were 21% and 5%, respectively, in older patients and 16% and 5%, respectively, in younger patients (each P value > .1). The rate of infection was 18% per cycle in older patients and 15% per cycle in younger patients (P = .2), with no difference noted in severity. Other organ toxicities were uncommon and showed no difference between age groups. The treatment-related mortality rate was <1% in both cohorts (P > .5). In multivariate analysis, increasing age and performance status influenced the incidence of hematologic toxicity, whereas only performance status influenced the rate of infection and severe infection.
  
  
  CONCLUSIONS
  Fludarabine-based combination chemotherapy regimens were well tolerated and can be delivered safely to older patients who have a good performance status with modestly increased myelosuppression but no increase in severe infectious complications or treatment-related mortality.
authors.affiliation: Department of Hematology, The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Alvin
authors.initials: A
authors.lastname: Milner
authors.forename: E Henry
authors.initials: EH
authors.lastname: Januszewicz
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: David
authors.initials: D
authors.lastname: Westerman
authors.forename: Max M
authors.initials: MM
authors.lastname: Wolf
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D012307:Risk Factors; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine