Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium

N Engl J Med. 1988 Jun 2;318(22):1414-22. doi: 10.1056/NEJM198806023182202.


We evaluated the ability of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to prevent chemotherapy-induced neutropenia or to accelerate recovery from this complication and thus allow patients to receive full doses of antineoplastic agents on time, according to protocol design. Twenty-seven patients with transitional-cell carcinoma of the urothelium who were undergoing treatment with methotrexate, doxorubicin, vinblastine, and cisplatin were given rhG-CSF (up to 60 micrograms per kilogram of body weight per day) before their first cycle of combination chemotherapy, during the first cycle, or at both points. Treatment with rhG-CSF before chemotherapy resulted in a dose-dependent increase in the absolute neutrophil count. Treatment with rhG-CSF after chemotherapy significantly reduced the number of days (91 percent) per patient on which the absolute neutrophil count was 1000 per microliter or less (P = 0.0039), reduced the number of days (1 vs. 35) on which antibiotics were used to treat fever and neutropenia, and significantly increased the percentage (100 vs. 29 percent) of patients qualified to receive planned chemotherapy on day 14 of the treatment cycle (P = 0.0015). In addition, the incidence of mucositis was significantly decreased (11 vs. 44 percent, P = 0.041), as was its severity. These findings demonstrate that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation. In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Agranulocytosis / prevention & control*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Transitional Cell / drug therapy*
  • Cisplatin / administration & dosage
  • Colony-Stimulating Factors / administration & dosage
  • Colony-Stimulating Factors / therapeutic use*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Drug Tolerance
  • Female
  • Granulocyte Colony-Stimulating Factor
  • Humans
  • Leukocyte Count
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neutropenia / prevention & control*
  • Neutropenia / therapy
  • Neutrophils
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Urinary Bladder Neoplasms / drug therapy*
  • Vinblastine / administration & dosage


  • Colony-Stimulating Factors
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Vinblastine
  • Doxorubicin
  • Cisplatin
  • Methotrexate