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    Growth factor-assisted chemotherapy--the Manchester experience.

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    Authors
    Crowther, Derek
    Scarffe, J Howard
    Howell, Anthony
    Thatcher, Nick
    Bronchud, M
    Steward, William P
    Testa, Nydia G
    Dexter, T Michael
    Affiliation
    Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
    Issue Date
    1990
    
    Metadata
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    Abstract
    Stimulation of red cell production by erythropoietin and of granulocyte production by granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-CSF (GM-CSF) has been demonstrated in several clinical studies. The first study to show that a human CSF could be used to shorten the period of neutropenia and reduce the risk of serious infection following intensive combination chemotherapy was carried out in Manchester using G-CSF. The period of neutropenia was significantly shortenened (by a median of 80%) and the neutrophil count levels were restored and above normal by 14 days after chemotherapy. In view of these results a further study was undertaken to examine the possibility of using intensive two weekly chemotherapy under cover of G-CSF. Treatment with Doxorubicin at doses of 75, 100, 125 and 150 mg/m2 was followed by infusion of G-CSF for 11 days. The neutrophil counts returned to normal within 12-14 days, allowing the delivery of up to three cycles of high dose chemotherapy at 14 day intervals. These studies demonstrated that intensive chemotherapy with dose-limiting myelodepression can be given with increased frequency under cover of G-CSF. Our studies using GM-CSF have also shown that administration by continuous i.v. infusion can reduce the period of life-threatening neutropenia following high dose Melphalan (120 mg/m2) without resort to autologous bone marrow transplantation (ABMT). In this study the period of granulocytopenia following Melphalan (less than 500 g x 10(9)/m2) was less than 15 days. This compares favourably with other series using high dose Melphalan followed by ABMT without CSF, where the duration of severe neutropenia was prolonged beyond three weeks. Although it appears that G-CSF and GM-CSF should be given either by continuous i.v. infusion or s.c. injection at doses between 3-10 micrograms/kg/day to obtain maximum biological effect, a great deal more work is required to determine optimum schedules and investigate the possibility of using more than one bioregulator.
    Citation
    Growth factor-assisted chemotherapy--the Manchester experience. 1990, 148:201-10; discussion 211-4 Ciba Found Symp
    Journal
    Ciba Foundation Symposium
    URI
    http://hdl.handle.net/10541/108139
    PubMed ID
    1690624
    Type
    Article
    Language
    en
    ISSN
    0300-5208
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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