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

J Clin Oncol. 2004 Jul 1;22(13):2587-93. doi: 10.1200/JCO.2004.08.125.

Abstract

Purpose: 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).

Patients and 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.

Conclusion: 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.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Docetaxel
  • Doxorubicin / administration & dosage*
  • Doxorubicin / adverse effects*
  • Doxorubicin / pharmacology
  • Drug Administration Schedule
  • Female
  • Fever / chemically induced
  • Humans
  • Infusions, Intravenous
  • Middle Aged
  • Neoplasm Metastasis
  • Neutropenia / chemically induced*
  • Taxoids / administration & dosage*
  • Taxoids / adverse effects*
  • Taxoids / pharmacology
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Taxoids
  • Docetaxel
  • Doxorubicin