Effects of recombinant human granulocyte-macrophage colony-stimulating factor on myelosuppression induced by multiple cycles of high-dose chemotherapy in patients with advanced breast cancer

Klaas Hoekman, John Wagstaff, Cees J. Van Groeningen, Jan B. Vermorken, Epie Boven, Herbert M. Pinedo

Research output: Contribution to journalArticle

Abstract

In this study, 18 patients with advanced breast cancer were treated with multiple cycles of doxorubicin (75 or 90 mg/m2) plus cyclophosphamide (750 or 1000 mg/m2) every 21 days. Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 μg/m2 per day) was administered by continuous infusion during 10 days (days 2-12), starting in the first or second cycle of chemotherapy. Sixteen (89%) of 18 patients (95% confidence interval, 65%-99%) achieved an objective remission, five (28%) of which were complete. The median duration of response was 7 months. When GM-CSF was used for the first time, it had an effect on the kinetics of all blood cells, including neutrophils, lymphocytes, thrombocytes, and reticulocytes. However, in subsequent cycles of chemotherapy, the stimulatory effect of GM-CSF on hematopoiesis was substantially diminished. World Health Organization grade 3 and 4 neutropenia and thrombocytopenia necessitated dose reductions of doxorubicin and cyclophosphamide from cycle 2 onward in all patients treated with the highest dose. Side effects of GM-CSF included fever, general weakness, and hypotension. These toxic effects mimicked sepsis, and hospital admission for treatment with intravenous antibiotics was required for 73 days in 61 cycles of chemotherapy that included GM-CSF. Dose-intensive chemotherapy produced a high response rate in patients with advanced breast cancer. However, GM-CSF administered from day 2 to day 12 at a dose of 250 μg/m2. per day by continuous infusion did not adequately ameliorate the myelosuppression induced by repeated cycles of dose-intensive chemotherapy.

Original languageEnglish (US)
Pages (from-to)1546-1553
Number of pages8
JournalJournal of the National Cancer Institute
Volume83
Issue number21
StatePublished - Nov 6 1991
Externally publishedYes

Fingerprint

Macrophage
Chemotherapy
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Breast Cancer
Dose
Breast Neoplasms
Cycle
Drug Therapy
Doxorubicin
Cyclophosphamide
Hematopoiesis
Neutrophils
Lymphocytes
Poisons
Reticulocytes
Antibiotics
Neutropenia
Hypotension
Blood

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Effects of recombinant human granulocyte-macrophage colony-stimulating factor on myelosuppression induced by multiple cycles of high-dose chemotherapy in patients with advanced breast cancer. / Hoekman, Klaas; Wagstaff, John; Van Groeningen, Cees J.; Vermorken, Jan B.; Boven, Epie; Pinedo, Herbert M.

In: Journal of the National Cancer Institute, Vol. 83, No. 21, 06.11.1991, p. 1546-1553.

Research output: Contribution to journalArticle

Hoekman, Klaas ; Wagstaff, John ; Van Groeningen, Cees J. ; Vermorken, Jan B. ; Boven, Epie ; Pinedo, Herbert M. / Effects of recombinant human granulocyte-macrophage colony-stimulating factor on myelosuppression induced by multiple cycles of high-dose chemotherapy in patients with advanced breast cancer. In: Journal of the National Cancer Institute. 1991 ; Vol. 83, No. 21. pp. 1546-1553.
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