title: Observational study of the prevalence of febrile neutropenia in patients who received filgrastim or pegfilgrastim associated with 3-4 week chemotherapy regimens in community oncology practices.
abstract: BACKGROUND
  Colony-stimulating factors (CSFs) significantly decrease the risk of febrile neutropenia (FN), a common complication of myelosuppressive chemotherapy. Pegfilgrastim (6 mg), introduced in 2002, has a sustained duration of action, with a single dose comparable in efficacy to daily injections of filgrastim (5 g per kg per day) for 10 to 11 days; both agents should be initiated 24 hours after completing chemotherapy.
  
  
  OBJECTIVE
  To (1) describe the use of pegfilgrastim and filgrastim in oncology practices throughout the United States and (2) compare their effectiveness in actual practice as measured by the outcome of febrile neutropenia in patients who received chemotherapy regimens administered every 3 to 4 weeks for breast, lung, ovarian, colon cancer, or lymphoma and who received a CSF prior to developing FN.
  
  
  METHODS
  Data were retrospectively obtained from the medical records of a cohort of adult patients aged 18 years or older treated in 99 community oncology practices in the United States in 2001 and 2003. Eligible patients were treated with chemotherapy every 3 to 4 weeks for breast, lung, ovarian, colon cancer, or lymphoma and were users of filgrastim in 2001 (prior to the U.S. Food and Drug Administration approval of pegfilgrastim in January 2002) or users of either filgrastim or pegfilgrastim or both CSF agents in 2003.
  
  
  RESULTS
  Pegfilgrastim was initiated, on average, 2.4 days (SD +/-3.2) after chemotherapy in the first cycle of use and 1.9 (+/-3.0) days in subsequent cycles of use. In contrast, filgrastim was started on average 7.7 (+/-6.5) days and 4.9 (4.6) days after chemotherapy in the first and subsequent cycles of use in 2001, increasing to 9.6 (+/-6.2) and 6.4 (+/-6.4) days in 2003. In the first cycle of CSF use, filgrastim was administered for an average of 5.2 (+/-3.5) days to 583 patients in 2001 and 3.7 (+/-2.8) days to 868 patients in 2003 (P <0.001). Among patients who received more than 1 cycle of filgrastim (n = 457 in 2001 and n = 489 in 2003; 78.4% and 56.3% of filgrastim users, respectively), the mean days of filgrastim administered in subsequent cycles was 6.0 (+/-3.5) in 2001 and 4.6 (+/-3.2) in 2003. Pegfilgrastim was administered as a single dose per chemotherapy course to 1,412 patients in 2003. Patients who received pegfilgrastim were more likely to have at least 1 myelosuppressive drug (74.8%) in the regimen compared with patients who received filgrastim in 2003 (70.0%, P = 0.013), but a greater proportion of filgrastim patients in 2003 (19.4%) had advanced-stage disease compared with pegfilgrastim patients (14.8%, P = 0.005). More patients who received filgrastim in 2003 (36.2%) had a cancer other than breast cancer or non-Hodgkin's lymphoma compared with those who received pegfilgrastim (29.5%, P = 0.001). A total of 94 of 1,451 patients (6.5%) who received filgrastim experienced FN compared with 67 of 1,412 patients (4.7%) for pegfilgrastim. The odds ratio of developing FN among patients who received filgrastim versus pegfilgrastim was 1.41 (95% confidence interval, 1.02-1.96; P = 0.040) after adjusting for patient and chemotherapy regimen characteristics.
  
  
  CONCLUSIONS
  In this retrospective study of patients treated in 99 community oncology practices, patients who received filgrastim often initiated treatment later than recommended and received fewer days per cycle than demonstrated to be effective in randomized controlled trials. Pegfilgrastim was generally initiated earlier within the course of chemotherapy compared with filgrastim, and because of its sustained duration of action, only a single injection was required. In these patients treated with a heterogeneous group of chemotherapy regimens with a broad range of risk of FN, overall, an absolute 1.8% increase in the incidence of developing FN was observed in patients who received filgrastim compared with patients who received pegfilgrastim, (absolute rates of 6.5% and 4.7%, respectively).
authors.affiliation: Hematology/Oncology, VA Medical Center, Minneapolis, MN 55417, USA. morri002@umn.edu
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Morrison
authors.forename: Mitchell
authors.initials: M
authors.lastname: Wong
authors.forename: Dawn
authors.initials: D
authors.lastname: Hershman
authors.forename: Luis T
authors.initials: LT
authors.lastname: Campos
authors.forename: Beiying
authors.initials: B
authors.lastname: Ding
authors.forename: Jennifer
authors.initials: J
authors.lastname: Malin
mesh_terms: D000368:Aged; D003153:Community Health Services; D004358:Drug Therapy; D005260:Female; D005334:Fever / Q000453:epidemiology*; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008485:Medical Audit; D008495:Medical Oncology; D008875:Middle Aged; D009503:Neutropenia / Q000453:epidemiology*; D017063:Outcome Assessment, Health Care; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim