Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors

  • Authors:
    • M Danova
    • G Mazzini
    • R Alberici
    • C Lucotti
    • S Palmeri
    • G Fincato
    • M Cazzola
    • A Riccardi
    • E Ascari
  • View Affiliations

  • Published online on: November 1, 1996     https://doi.org/10.3892/ijo.9.5.971
  • Pages: 971-976
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Abstract

The biological mechanisms by which the association of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is expected to effectively reduce the hematological toxicity associated with chemotherapy (CT) are not completely elucidated. We exploited the cell kinetic changes of the bone marrow CD34(+) cell subset after CT followed by the IL-3+GM-CSF together with the clinical effects of this association. Eighteen patients with advanced cancers and normal hematopoiesis were treated with an intensified CT course (mg/m(2): CTX 1100, epirubicin 100, VP-16 200; iv day 1). Six cycles were planned at 14-day intervals with the support of IL-3 (5 mu g/kg/day; from day 2 to 6) sequenced with GM-CSF (same dose; from day 7 to 11). DNA content and bromodeoxyuridine incorporation were evaluated using flow cytometry on immunomagnetically-sorted bone marrow CD34(+) cells, at baseline and at different times (days 5, 6, 7, 8, 11 and 14) after CT followed by IL-3+GM-CSF. Treatment with IL-3 induced a marked increase in the % of myeloid precursors with respect to the baseline and in the % of CD34(+) cells in S-phase. However, while the first parameter remained elevated until day 14, the enhanced proliferative activity of the CD34(+) cell subset decreased after IL-3 was stopped and remained significantly low during GM-CSF administration. These data suggest a negative rebound effect on CD34(+) cell proliferation after IL-3 discontinuation which is maintained during GMCSF, that led to kinetic refractoriness of the hyperplastic marrow. In the 99 courses completed a rapid neutrophil and platelet recovery was obtained without cumulative multilineage toxicity. The modifications of CD34(+) cell cycling after CT followed by IL-3+GM-CSF could provide additional myeloprotection during multicyclic, dose-intensive programs.

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November 1996
Volume 9 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Danova M, Mazzini G, Alberici R, Lucotti C, Palmeri S, Fincato G, Cazzola M, Riccardi A and Ascari E: Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors. Int J Oncol 9: 971-976, 1996
APA
Danova, M., Mazzini, G., Alberici, R., Lucotti, C., Palmeri, S., Fincato, G. ... Ascari, E. (1996). Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors. International Journal of Oncology, 9, 971-976. https://doi.org/10.3892/ijo.9.5.971
MLA
Danova, M., Mazzini, G., Alberici, R., Lucotti, C., Palmeri, S., Fincato, G., Cazzola, M., Riccardi, A., Ascari, E."Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors". International Journal of Oncology 9.5 (1996): 971-976.
Chicago
Danova, M., Mazzini, G., Alberici, R., Lucotti, C., Palmeri, S., Fincato, G., Cazzola, M., Riccardi, A., Ascari, E."Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors". International Journal of Oncology 9, no. 5 (1996): 971-976. https://doi.org/10.3892/ijo.9.5.971