Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study

Ann Oncol. 2008 Feb;19(2):292-8. doi: 10.1093/annonc/mdm438. Epub 2007 Sep 9.

Abstract

Background: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC.

Patients and methods: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles).

Results: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events.

Conclusion: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Ciprofloxacin / administration & dosage*
  • Ciprofloxacin / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Administration Schedule
  • Female
  • Filgrastim
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Neutropenia / chemically induced
  • Neutropenia / prevention & control*
  • Pilot Projects
  • Polyethylene Glycols
  • Probability
  • Recombinant Proteins
  • Survival Analysis
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Treatment Outcome

Substances

  • Recombinant Proteins
  • Taxoids
  • Granulocyte Colony-Stimulating Factor
  • pegfilgrastim
  • Polyethylene Glycols
  • Ciprofloxacin
  • Doxorubicin
  • Cyclophosphamide
  • Filgrastim

Supplementary concepts

  • TAC protocol