A phase I toxicity and feasibility trial of sequential dose-dense induction chemotherapy with doxorubicin, paclitaxel, and 5-fluorouracil followed by high dose consolidation for high-risk primary breast cancer

Leisha A. Emens, M. John Kennedy, John H. Fetting, Nancy E. Davidson, Elizabeth Garrett, Deborah K. Armstrong

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. We studied sequential dose-dense doxorubicin, paclitaxel, and 5-fluorouracil (A-T-F) before high dose chemotherapy (HDC) with autologous peripheral blood stem cell support (PBSCT). Our aims were to determine the maximum tolerated dose (MTD) of 5-FU in the dose-dense regimen and to determine the impact of dose-dense chemotherapy on HDC/PBSCT. Methods. Patients with Stage IIIB or Stage II or IIIA breast cancer with ≥4 involved ipsilateral lymph nodes were treated with nine cycles of chemotherapy at 14-day intervals. The regimen was doxorubicin at 80 mg/m2 x 3, followed by paclitaxel at 140 mg/m2 over 96 h x 3, then 5-FU at doses of 1285, 1470, or 1655 mg/m2 by continuous intravenous infusion over 72 h x 3. Patients then underwent a G-CSF-stimulated peripheral blood stem cell (PBSC) apheresis prior to receiving HDC with autologous PBSCT. Results. We identified 1285 mg/m2 as the MTD of 5-FU in this regimen. 5-FU-related DLTs included hand-foot syndrome, mucositis, and facial edema with somnolence. Unexpectedly, 3/19 treated patients developed congestive heart failure that prevented planned HDC. Compared to standard dose doxorubicin-containing adjuvant therapy, the dose-dense regimen also decreased CD34+ PBSC yields by about 40% (p = 0.049), requiring that 50% of patients have a supplemental bone marrow harvest. There was no difference in time to neutrophil, platelet, and red blood cell recovery after HDC. Conclusions. This regimen resulted in an unacceptably high rate of cardiac toxicity and is not recommended for further testing. It may be feasible to use a different schedule of 5-FU-containing dose-dense chemotherapy, particularly for the induction therapy of high-risk primary breast cancer prior to novel targeted therapies.

Original languageEnglish (US)
Pages (from-to)145-156
Number of pages12
JournalBreast Cancer Research and Treatment
Volume76
Issue number2
DOIs
StatePublished - Nov 1 2002

Keywords

  • Cardiotoxicity
  • Dose-dense therapy
  • Doxorubicin
  • Fluoropyrimidines
  • High dose therapy
  • Paclitaxel
  • Peripheral blood stem cell support

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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