This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Haan, G. Articles by Nijhof, W. Search for Related Content PubMed PubMed Citation Articles by de Haan, G. Articles by Nijhof, W.

Hemotoxicity by Prolonged Etoposide Administration to Mice Can Be Prevented by Simultaneous Growth Factor Therapy¹

Groningen Institute for Drug Studies, Department of Hematology, University of Groningen, Bloemsingel 10, 9712 KZ Groningen, the Netherlands [G. d. H., B. D., W. N.], and Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany [C. E., M. L.]

In this study, we determined in vivo interactions between hemopoietic growth factors and etoposide (VP-16) to assess whether normal blood cell production could be maintained during chemotherapy if hemopoietic growth factors were simultaneously administered. Groups of mice were treated for 7 consecutive days with four different doses of VP-16 in combination with three different doses of erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). In total, 12 combinations of VP-16 plus EPO and 12 combinations of VP-16 plus G-CSF were thus evaluated. Intricate dose-response surfaces of the effects of the different treatments on colony-forming units-erythroid, reticulocytes, hematocrit, colony-forming units-granulocyte/macrophage, and absolute neutrophil count were obtained, which revealed that: (a) simultaneous EPO administration was able to maintain reticulocyte production and to protect mice from VP-16 induced anemia; (b) simultaneous G-CSF administration was able to maintain granulocyte production and to protect mice from VP-16 induced neutropenia; (c) VP-16 dose escalation was feasible when EPO or G-CSF were simultaneously administered; and (d) no increased myelotoxicity on erythroid or granuloid progenitors was observed when EPO or G-CSF was simultaneously administered with VP-16. These results suggest that in vivo either individual hemopoietic progenitors can become resistant against VP-16-induced cell death by appropriate simultaneous growth factor administration or that the loss of overall cell amplification, induced by VP-16, can be compensated by extra amplification of surviving progenitors. Furthermore, these data indicate that a strict separation in time of cytostatic drug and growth factor treatment is not necessarily the optimal schedule with respect to the reduction of hemotoxicity.

¹ This work was partially sponsored by the Deutsche Forschungsgemeinschaft (Lo 342-5/1).

² To whom requests for reprints should be addressed.

Received 8/ 9/94. Accepted 11/11/94.

This article has been cited by other articles:

				A. Villunger, L. A. O'Reilly, N. Holler, J. Adams, and A. Strasser FAS Ligand, Bcl-2, Granulocyte Colony-Stimulating Factor, and p38 Mitogen-Activated Protein Kinase: Regulators of Distinct Cell Death and Survival Pathways in Granulocytes J. Exp. Med., September 5, 2000; 192(5): 647 - 658. [Abstract] [Full Text] [PDF]

				I. Roeder, G. de Haan, C. Engel, W. Nijhof, B. Dontje, and M. Loeffler Interactions of Erythropoietin, Granulocyte Colony-Stimulating Factor, Stem Cell Factor, and Interleukin-11 on Murine Hematopoiesis During Simultaneous Administration Blood, May 1, 1998; 91(9): 3222 - 3229. [Abstract] [Full Text] [PDF]