Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Oct;78(7):928–932. doi: 10.1038/bjc.1998.603

High-dose etoposide with granulocyte colony-stimulating factor for mobilization of peripheral blood progenitor cells: efficacy and toxicity at three dose levels.

E J Kanfer 1, D McGuigan 1, D Samson 1, Z Abboudi 1, G Abrahamson 1, J F Apperley 1, S Chilcott 1, C Craddock 1, J Davis 1, C MacDonald 1, D Macdonald 1, E Olavarria 1, N Philpott 1, G J Rustin 1, M J Seckl 1, M Sekhar 1, S Stern 1, E S Newlands 1
PMCID: PMC2063139  PMID: 9764585

Abstract

High-dose etoposide (2.0-2.4 g m(-2)) with granulocyte colony-stimulating factor (G-CSF) is an effective strategy to mobilize peripheral blood progenitor cells (PBPCs), although in some patients this is associated with significant toxicity. Sixty-three patients with malignancy were enrolled into this non-randomized sequential study. The majority (55/63, 87%) had received at least two prior regimens of chemotherapy, and seven patients had previously failed to mobilize following high-dose cyclophosphamide with G-CSF. Consecutive patient groups received etoposide at three dose levels [2.0 g m(-2) (n = 22), 1.8 g m(-2) (n = 20) and 1.6 g m(-2) (n = 21)] followed by daily G-CSF. Subsequent leukaphereses were assayed for CD34+ cell content, with a target total collection of 2.0 x 10(6) CD34+ cells kg(-1). Toxicity was assessed by the development of significant mucositis, the requirement for parenteral antibiotics or blood component support and rehospitalization incidence. Ten patients (16%) had less than the minimum target yield collected. Median collections in the three groups were 4.7 (2 g m(-2)), 5.7 (1.8 g m(-2)) and 6.5 (1.6 g m(-2)) x 10(6) CD34+ cells kg(-1). Five of the seven patients who had previously failed cyclophosphamide mobilization achieved more than the target yield. Rehospitalization incidence was significantly lower in patients receiving 1.6 g m(-2) etoposide than in those receiving 2.0 g m(-2) (P = 0.03). These data suggest that high-dose etoposide with G-CSF is an efficient mobilization regimen in the majority of heavily pretreated patients, including those who have previously failed on high-dose cyclophosphamide with G-CSF. An etoposide dose of 1.6 g m(-2) appears to be as effective as higher doses but less toxic.

Full text

PDF
928

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bezwoda W. R., Seymour L., Ariad S. High-dose etoposide in treatment of metastatic breast cancer. Oncology. 1992;49(2):104–107. doi: 10.1159/000227021. [DOI] [PubMed] [Google Scholar]
  2. Chao N. J., Schriber J. R., Grimes K., Long G. D., Negrin R. S., Raimondi C. M., Horning S. J., Brown S. L., Miller L., Blume K. G. Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy. Blood. 1993 Apr 15;81(8):2031–2035. [PubMed] [Google Scholar]
  3. Demirer T., Buckner C. D., Storer B., Lilleby K., Rowley S., Clift R., Appelbaum F. R., Storb R., Bensinger W. I. Effect of different chemotherapy regimens on peripheral-blood stem-cell collections in patients with breast cancer receiving granulocyte colony-stimulating factor. J Clin Oncol. 1997 Feb;15(2):684–690. doi: 10.1200/JCO.1997.15.2.684. [DOI] [PubMed] [Google Scholar]
  4. Dreger P., Klöss M., Petersen B., Haferlach T., Löffler H., Loeffler M., Schmitz N. Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts. Blood. 1995 Nov 15;86(10):3970–3978. [PubMed] [Google Scholar]
  5. Díaz-Mediavilla J., Llorente L., Martínez R., Alvarez-Carmona A., Jordá J., Del Potro E., González A., Morales D., Asenjo S., Fariñas M. Autotransplantation of peripheral blood stem cells mobilized by G-CSF in hematological malignancies: evidence for rapid and long-term sustained hematopoietic reconstitution. Leuk Lymphoma. 1996 Jan;20(3-4):327–332. doi: 10.3109/10428199609051626. [DOI] [PubMed] [Google Scholar]
  6. Elias A. D., Ayash L., Anderson K. C., Hunt M., Wheeler C., Schwartz G., Tepler I., Mazanet R., Lynch C., Pap S. Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer. Blood. 1992 Jun 1;79(11):3036–3044. [PubMed] [Google Scholar]
  7. Elliott C., Samson D. M., Armitage S., Lyttelton M. P., McGuigan D., Hargreaves R., Giles C., Abrahamson G., Abboudi Z., Brennan M. When to harvest peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood. J Clin Oncol. 1996 Mar;14(3):970–973. doi: 10.1200/JCO.1996.14.3.970. [DOI] [PubMed] [Google Scholar]
  8. Gianni A. M., Bregni M., Siena S., Magni M., Di Nicola M., Lombardi F., Tarella C., Pileri A., Bonadonna G. Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients. J Clin Oncol. 1992 Dec;10(12):1955–1962. doi: 10.1200/JCO.1992.10.12.1955. [DOI] [PubMed] [Google Scholar]
  9. Gianni A. M., Siena S., Bregni M., Tarella C., Stern A. C., Pileri A., Bonadonna G. Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation. Lancet. 1989 Sep 9;2(8663):580–585. doi: 10.1016/s0140-6736(89)90711-3. [DOI] [PubMed] [Google Scholar]
  10. Haas R., Möhle R., Frühauf S., Goldschmidt H., Witt B., Flentje M., Wannenmacher M., Hunstein W. Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood. 1994 Jun 15;83(12):3787–3794. [PubMed] [Google Scholar]
  11. Herzig R. H. High-dose etoposide and marrow transplantation. Cancer. 1991 Jan 1;67(1 Suppl):292–298. doi: 10.1002/1097-0142(19910101)67:1+<292::aid-cncr2820671314>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  12. Lie A. K., Rawling T. P., Bayly J. L., To L. B. Progenitor cell yield in sequential blood stem cell mobilization in the same patients: insights into chemotherapy dose escalation and combination of haemopoietic growth factor and chemotherapy. Br J Haematol. 1996 Oct;95(1):39–44. doi: 10.1046/j.1365-2141.1996.7442370.x. [DOI] [PubMed] [Google Scholar]
  13. Marangolo M., Rosti G., Amadori D., Leoni M., Ardizzone A., Fiorentini G., Cruciani G., Tienghi A., Ravaioli A., Sebastiani L. High-dose etoposide and autologous bone marrow transplantation as intensification treatment in small cell lung cancer: a pilot study. Bone Marrow Transplant. 1989 Jul;4(4):405–408. [PubMed] [Google Scholar]
  14. McQuaker I. G., Haynes A. P., Stainer C., Anderson S., Russell N. H. Stem cell mobilization in resistant or relapsed lymphoma: superior yield of progenitor cells following a salvage regimen comprising ifosphamide, etoposide and epirubicin compared to intermediate-dose cyclophosphamide. Br J Haematol. 1997 Jul;98(1):228–233. doi: 10.1046/j.1365-2141.1997.1812998.x. [DOI] [PubMed] [Google Scholar]
  15. Mross K., Bewermeier P., Krüger W., Stockschläder M., Zander A., Hossfeld D. K. Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies. J Clin Oncol. 1994 Jul;12(7):1468–1474. doi: 10.1200/JCO.1994.12.7.1468. [DOI] [PubMed] [Google Scholar]
  16. Postmus P. E., Mulder N. H., Sleijfer D. T., Meinesz A. F., Vriesendorp R., de Vries E. G. High-dose etoposide for refractory malignancies: a phase I study. Cancer Treat Rep. 1984 Dec;68(12):1471–1474. [PubMed] [Google Scholar]
  17. Richman C. M., Weiner R. S., Yankee R. A. Increase in circulating stem cells following chemotherapy in man. Blood. 1976 Jun;47(6):1031–1039. [PubMed] [Google Scholar]
  18. Rosenfeld C. S., Bolwell B., LeFever A., Taylor R., List A., Fay J., Collins R., Andrews F., Pallansch P., Schuster M. W. Comparison of four cytokine regimens for mobilization of peripheral blood stem cells: IL-3 alone and combined with GM-CSF or G-CSF. Bone Marrow Transplant. 1996 Feb;17(2):179–183. [PubMed] [Google Scholar]
  19. Schmitz N., Linch D. C., Dreger P., Goldstone A. H., Boogaerts M. A., Ferrant A., Demuynck H. M., Link H., Zander A., Barge A. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996 Feb 10;347(8998):353–357. doi: 10.1016/s0140-6736(96)90536-x. [DOI] [PubMed] [Google Scholar]
  20. Schwartzberg L. S., Birch R., Hazelton B., Tauer K. W., Lee P., Jr, Altemose R., George C., Blanco R., Wittlin F., Cohen J. Peripheral blood stem cell mobilization by chemotherapy with and without recombinant human granulocyte colony-stimulating factor. J Hematother. 1992 Winter;1(4):317–327. doi: 10.1089/scd.1.1992.1.317. [DOI] [PubMed] [Google Scholar]
  21. Sutherland D. R., Keating A., Nayar R., Anania S., Stewart A. K. Sensitive detection and enumeration of CD34+ cells in peripheral and cord blood by flow cytometry. Exp Hematol. 1994 Sep;22(10):1003–1010. [PubMed] [Google Scholar]
  22. To L. B., Roberts M. M., Haylock D. N., Dyson P. G., Branford A. L., Thorp D., Ho J. Q., Dart G. W., Horvath N., Davy M. L. Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant. 1992 Apr;9(4):277–284. [PubMed] [Google Scholar]
  23. To L. B., Shepperd K. M., Haylock D. N., Dyson P. G., Charles P., Thorp D. L., Dale B. M., Dart G. W., Roberts M. M., Sage R. E. Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood. Exp Hematol. 1990 Jun;18(5):442–447. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES