title: Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer.
abstract: BACKGROUND
  Adjuvant chemotherapy with new cytotoxic agents for breast cancer must be properly assessed for toxicity.
  
  
  OBJECTIVE
  To describe adverse events associated with adjuvant chemotherapy for breast cancer, which led to premature termination of a clinical trial.
  
  
  METHODS
  We conducted a prospective randomized multicenter study (Reposant sur des Arguments Pronostiques et Predictifs [RAPP]-01) to compare the effectiveness of 2 chemotherapy regimens. Patients (women aged 18-70 years) had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes (< or =3) or no positive axillary lymph nodes (N0), but were at a high risk of relapse. Patients were treated at 11 French cancer referral centers from June 1999 through January 2003. Primary prophylaxis for febrile neutropenia was not recommended in the study protocol.
  
  
  METHODS
  Doxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2, or doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, given postoperatively for 4 courses.
  
  
  METHODS
  The main end point was the disease-free survival rate at 5 years, as estimated using the Kaplan-Meier product limit method. Secondary end points included safety, which is the focus of this article, and overall survival.
  
  
  RESULTS
  A total of 627 women were enrolled. Median follow-up is currently too short (24 months) to analyze the primary end point. The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of perforative peritonitis occurred among patients with febrile neutropenia, all in the doxorubicin-docetaxel group. The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen (40.8%) than with the doxorubicin-cyclophosphamide regimen (7.1%) (P<.001).
  
  
  CONCLUSIONS
  A high risk of life-threatening complications associated with the doxorubicin-docetaxel regimen was found in this open-label controlled trial. The doxorubicin-docetaxel combination should not be considered as an alternative to the doxorubicin-cyclophosphamide regimen outside carefully designed studies that include primary prophylaxis for febrile neutropenia.
authors.affiliation: Department of Medical Oncology, René Huguenin Cancer Centre, Saint-Cloud, France. e.brain@stcloud-huguenin.org
authors.forename: Etienne G C
authors.initials: EG
authors.lastname: Brain
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Daniel
authors.initials: D
authors.lastname: Serin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Kirscher
authors.forename: Yvon
authors.initials: Y
authors.lastname: Graic
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Eymard
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Extra
authors.forename: Martin
authors.initials: M
authors.lastname: Combe
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fourme
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Jacques
authors.initials: J
authors.lastname: Rouëssé
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D018805:Sepsis / Q000209:etiology*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin