title: Multicenter randomized trial comparing sequential with concomitant administration of doxorubicin and docetaxel as first-line treatment of metastatic breast cancer: a Spanish Breast Cancer Research Group (GEICAM-9903) phase III study.
abstract: OBJECTIVE
  This randomized, multicenter, phase III trial evaluated whether sequential doxorubicin and docetaxel (A-->T) reduced hematological toxicity, especially febrile neutropenia, compared with concomitant (AT) administration as first-line chemotherapy in metastatic breast cancer (MBC).
  
  
  METHODS
  One hundred forty-four patients were randomly assigned to receive three cycles of doxorubicin 75 mg/m(2) every 21 days followed by three cycles of docetaxel 100 mg/m(2), every 21 days (A-->T) or six cycles of the combination doxorubicin 50 mg/m(2) and docetaxel 75 mg/m(2) (AT) every 21 days. Patients previously treated with anthracyclines received two cycles of doxorubicin followed by four cycles of docetaxel (A-->T), or three cycles of AT followed by three cycles of docetaxel 100 mg/m(2) every 21 days.
  
  
  RESULTS
  Febrile neutropenia was less common in the A-->T arm (29.3% of patients, 6.9% of cycles) compared with the AT arm (47.8% of patients, 14.8% of cycles; P =.02 and P =.0004, respectively). Asthenia, diarrhea, and fever occurred more frequently in the AT arm. The overall responses rates were 61% in the A-->T arm (95% CI, 50% to 72%) and 51% in the AT arm (95% CI, 39% to 63%). The median duration of response was 8.7 months (A-->T) and 7.6 months (AT); the median time to progression was 10.5 months (A-->T) and 9.2 months (AT); the median overall survival was 22.3 months (A-->T) and 21.8 months (AT); and no significant differences were found.
  
  
  CONCLUSIONS
  A-->T significantly reduced febrile neutropenia compared with AT in MBC patients and maintains comparable antitumoral efficacy. A-->T represents a valid option for the treatment of MBC.
authors.affiliation: Medical Oncology Department, Complejo Hospitalario Virgen de la Victoria, Málaga, Spain. oncologia98@yahoo.com
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos
authors.forename: Encarna
authors.initials: E
authors.lastname: Adrover
authors.forename: Ana
authors.initials: A
authors.lastname: Balil
authors.forename: Carlos
authors.initials: C
authors.lastname: Jara
authors.forename: Agustí
authors.initials: A
authors.lastname: Barnadas
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Aramburo
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.forename: Margarita
authors.initials: M
authors.lastname: Amenedo
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced*; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin