title: The impact of chemotherapy dose intensity and supportive care on the risk of febrile neutropenia in patients with early stage breast cancer: a prospective cohort study.
abstract: BACKGROUND
  Febrile neutropenia (FN) is a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. This study evaluated the time course of neutropenic events and patterns of supportive care interventions in patients receiving chemotherapy for early-stage breast cancer treated in oncology community practices.
  
  
  METHODS
  A prospective cohort study of adult cancer patients initiating a new chemotherapy regimen was conducted at 115 US sites. Toxicity associated with chemotherapy including neutropenic and infectious complications was recorded over four cycles. Clinical interventions were recorded including reductions in chemotherapy dose intensity and use of supportive care measures.
  
  
  RESULTS
  A total of 1,202 patients with stage I-III breast cancer were evaluated. The majority of neutropenic (116 of 196) and infection events (179 of 325) occurred in the initial cycle. A decrease in occurrence of FN and infection was observed in the subsequent cycles, along with an increase in utilization of colony stimulating factors (CSFs), antibiotics and reductions in chemotherapy dose intensity. The overall risk of FN in all patients was 16.3%. In patients who started treatment at or near full dose intensity, the FN risk reached 21.0% without primary CSF prophylaxis and it was 9.0% with prophylaxis. There was no significant difference in FN rates by menopausal or hormone receptors status.
  
  
  CONCLUSIONS
  The risk of neutropenic complications is greatest in the initial cycle when most patients receive full-dose chemotherapy. A decrease in neutropenic events during subsequent cycles is associated with reduced dose intensity or increased use of supportive care measures. However, the cumulative risk of FN remains high in patients with early-stage breast cancer receiving full dose chemotherapy without prophylactic measures.
authors.affiliation: Fred Hutchinson Cancer Research Center, Hutchinson Institute for Cancer Outcomes Research, 1100 Fairview Avenue North, M3-B232, PO Box 19024, Seattle, WA 98109-1024 USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Culakova
authors.affiliation: Fred Hutchinson Cancer Research Center, Hutchinson Institute for Cancer Outcomes Research, 1100 Fairview Avenue North, M3-B232, PO Box 19024, Seattle, WA 98109-1024 USA.
authors.forename: Marek S
authors.initials: MS
authors.lastname: Poniewierski
authors.affiliation: Empire State College, Saratoga Springs, NY USA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Wolff
authors.affiliation: University of Washington, Seattle, WA USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Dale
authors.affiliation: Duke University, Durham, NC USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.affiliation: Fred Hutchinson Cancer Research Center, Hutchinson Institute for Cancer Outcomes Research, 1100 Fairview Avenue North, M3-B232, PO Box 19024, Seattle, WA 98109-1024 USA ; University of Washington, Seattle, WA USA.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Lyman
keywords: Chemotherapy; Infection; Toxicity neutropenia