Dose-intensive chemotherapy with doxorubicin, cyclophosphamide and GM-CSF fails to improve survival of metastatic breast cancer patients

A. H. Honkoop, K. Hoekman, J. Wagstaff, E. Boven, C. J. Van Groeningen, G. Giaccone, J. B. Vermerken, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: A dose response relationship for doxorubicin and cyclophosphamide has been suggested. In a previous dose finding study we treated advanced breast cancer patients with escalating doses of doxorubicin and cyclophosphamide in combination with GM-CSF. The aim of this study is to further define the acute and cumulative toxicity of this treatment in relation to its antitumor activity. Patients and methods: Twenty-eight patients with metastatic breast cancer were treated with doxorubicin (90 mg/m2) and cyclophosphamide (1000 mg/m2) at 3-week intervals. Dose reductions of 10% were applied in the second and fourth cycles. On the second day GM-CSF was started at 250 μg/m2 daily for 10 days. The intention was to give 6 cycles, but when a complete remission was reached earlier only one more cycle was given as consolidation. Results: The median number of cycles was 5 (range 2-6). Twenty-three patients responded (82%, 95% CI 69%-97%), with 9 of them achieving a complete response (32%, 95% CI 14%-50%). For the 18 patients evaluable for time to progression and survival the median time to progression was 8 months and the median survival 14.5 months. Toxicity was substantial: grades 3 or 4 neutropenia occurred in 95% of cycles and grades 3-4 thrombocytopenia in 49% of cycles. Grade 3-4 mucositis was present in 13% of the cycles. Weakness and fatigue were always present and were cumulative. Four patients had a decline in the left ventricular ejection fraction (LVEF). These side effects were the reason for discontinuing therapy in 9 of the 28 patients (32%). Conclusion. This treatment has a high response rate in comparison with conventional-dose chemotherapy but does not prolong time to progression or survival. The toxicity makes this protocol unsuitable for use as palliative treatment.

Original languageEnglish (US)
Pages (from-to)35-39
Number of pages5
JournalAnnals of Oncology
Issue number1
StatePublished - Jan 1996
Externally publishedYes


  • Breast cancer
  • Chemotherapy
  • Dose Intensity
  • GM-CSF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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