Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Conditioning Regimens

Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer

Bone Marrow Transplantation volume 25, pages 123–130 (2000)Cite this article

Abstract

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 × 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123–130.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bezwoda WR, Seymour L, Dansey RD . High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial J Clin Oncol 1995 13: 2483–2489

    Article  CAS  PubMed  Google Scholar 

  2. Stadtmauer EA, O'Neill A, Goldstein LJ et al. Phase III randomized trial of high dose chemotherapy (HDC) and stem cell support (SCT) shows no difference in overall survival or severe toxicity compared to maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for women with metastatic breast cancer who are responding to conventional induction chemotherapy: the Philadelphia Intergroup Study (PBT-1) Proc Am Soc Clin Oncol 1999 18: 1a

    Google Scholar 

  3. Antman KH, Rowlings PA, Vaughan WP et al. High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America J Clin Oncol 1997 15: 1870–1879

    Article  CAS  PubMed  Google Scholar 

  4. Siena S, Bregni M, Belli N et al. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients Blood 1991 77: 400–409

    CAS  PubMed  Google Scholar 

  5. Gregory CJ, Eaves AC . Human marrow cells capable of erythropoietic differentiation in vitro: definition of three eythroid colony responses Blood 1977 49: 855–864

    CAS  PubMed  Google Scholar 

  6. Miller AB, Hoogstraten B, Staguet M, Winkler A . Reporting results of cancer treatment Cancer 1981 47: 207–214

    Article  CAS  PubMed  Google Scholar 

  7. McCredie K, Hersh E, Friereich E . Cells capable of colony formation in the peripheral blood of man Science 1971 171: 293–294

    Article  CAS  PubMed  Google Scholar 

  8. Richman CM, Weiner RS, Yankee RA . Increase in circulating stem cells following chemotherapy in man Blood 1976 47: 1031–1039

    CAS  PubMed  Google Scholar 

  9. To LB, Haylock DN, Kimber RJ, Juttner CA . High levels of circulating hemopoietic stem cells in very early remission from acute non-lymphoblastic leukemia and their collection and preservation Br J Haematol 1984 58: 399–410

    Article  CAS  PubMed  Google Scholar 

  10. Henon PR, Butturini A, Gale RP . Blood-derived hematoipoietic cell transplants: blood to blood? Lancet 1991 337: 961–963

    Article  CAS  PubMed  Google Scholar 

  11. Lowry PA, Tabbara IA . Peripheral hematopoietic stem cell transplantation: current concepts Exp Hematol 1992 20: 937–942

    CAS  PubMed  Google Scholar 

  12. Gillespie TW, Hillyer CD . Peripheral blood progenitor cells for marrow reconstitution: mobilization and collectionstrategies Transfusion 1996 36: 611–624

    Article  CAS  PubMed  Google Scholar 

  13. To LB, Haylock DN, Simmons PJ, Juttner CA . The biology and clinical uses of blood stem cells Blood 1997 89: 2233–2258

    CAS  PubMed  Google Scholar 

  14. Moog R, Muller N . Technical aspects and performance in collecting peripheral blood progenitor cells Ann Hematol 1998 77: 143–147

    Article  CAS  PubMed  Google Scholar 

  15. Siena S, Bregni M, Brando M et al. Circulating CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte–macrophage colony-stimulating factor Blood 1989 74: 1905–1914

    CAS  PubMed  Google Scholar 

  16. To LB, Shepperd KM, Haylock DN et al. Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood Exp Hematol 1990 18: 442–447

    CAS  PubMed  Google Scholar 

  17. Tarella C, Ferrero D, Bregni M et al. Peripheral blood expansion of early progenitor cells after high-dose cyclophosphamide and rhGM-CSF Eur J Cancer 1991 27: 22–27

    Article  CAS  PubMed  Google Scholar 

  18. Demirer T, Buckner CD, Storer B et al. 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 15: 684–690

    Article  CAS  PubMed  Google Scholar 

  19. Demirer T, Rowley S . Buckner CD et al. Peripheral-blood stem-cell collections after paclitaxel, cyclophosphamide, and recombinant human granulocyte colony-stimulating factor in patients with breast and ovarian cancer J Clin Oncol 1995 13: 1714–1719

    Article  CAS  PubMed  Google Scholar 

  20. Socinski MA, Cannistra SA, Elias A et al. Granulocyte–macrophage colony stimulating factor expands the circulating hemopoietic progenitor cell compartment in man Lancet 1988 I: 1194–1198

    Article  Google Scholar 

  21. Haas R, Ho AD, Bredthauer U et al. Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte–macrophage colony stimulating factor Exp Hematol 1990 18: 94–98

    CAS  PubMed  Google Scholar 

  22. Sheridan WP, Begley CG, Juttner CA et al. Effect ofperipheral-blood progenitor cells mobilized by filgrastim(G-CSF) on platelet recovery after high-dose chemotherapy Lancet 1992 339: 640–644

    Article  CAS  PubMed  Google Scholar 

  23. Peters WP, Rosner G, Ross M et al. Comparative effects of granulocyte–macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy Blood 1993 81: 1709–1719

    CAS  PubMed  Google Scholar 

  24. Rosenfeld CS, Shadduck PK, Zeigler ZR et al. Cyclophosphamide mobilized peripheral blood stem cells in patients with lymphoid malignancies Bone Marrow Transplant 1995 15: 433–438

    CAS  PubMed  Google Scholar 

  25. Brugger W, Bross K, Frisch J et al. Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte–macrophage colony-stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin Blood 1992 79: 1193–1200

    CAS  PubMed  Google Scholar 

  26. Schneider JG, Crown JP, Wasserheit C et al. Factors affecting the mobilization of primitive and committed hematopoietic progenitors into the peripheral blood of cancer patients Bone Marrow Transplant 1994 14: 877–884

    CAS  PubMed  Google Scholar 

  27. Schimazaki C, Oku N, Ashihara E et al. Collection of peripheral blood stem cells mobilized by high-dose Ara-C plus VP-16 or aclarubicin followed by recominant human granulocyte-colony stimulating factor Bone Marrow Transplant 1992 10: 341–346

    Google Scholar 

  28. Menichella G, Pierelli L, Scambia G et al. Low-dose cyclophosphamide in combination with cisplatin or epirubicin plus rhG-CSF allows adequate collection of PBSC for autotransplantation during adjuvant therapy for high-risk cancer Bone Marrow Transplant 1994 14: 907–912

    CAS  PubMed  Google Scholar 

  29. Weaver CH, Schwartzberg LS, Birch R et al. Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor: an analysis of 497 patients Transfusion 1997 37: 896–903

    Article  CAS  PubMed  Google Scholar 

  30. Schwartzberg LS, Weaver CH, Birch R et al. A randomized trial of two doses of cyclophosphamide with etoposide and G-CSF for mobilization of peripheral blood stem cells in 318 patients with stage II–III breast cancer J Hematother 1998 7: 141–150

    Article  CAS  PubMed  Google Scholar 

  31. Steward DA, Guo D, Morris D et al. Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens Bone Marrow Transplant 1999 23: 111–117

    Article  Google Scholar 

  32. Bensinger W, Appelbaum F, Rowley S et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells J Clin Oncol 1995 13: 2547–2555

    Article  CAS  PubMed  Google Scholar 

  33. Weaver CH, Hazelton B, Birch R et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloblative chemotherapy Blood 1995 86: 3961–3969

    CAS  PubMed  Google Scholar 

  34. Olivieri A, Offidani M, Ciniero L et al. Optimization of the yield of PBSC for autotransplantation mobilized by high-dose chemotherapy and G-CSF: proposal for a mathematical model Bone Marrow Transplant 1994 14: 273–278

    CAS  PubMed  Google Scholar 

  35. Bensinger WI, Longin K, Appelbaum F et al. Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation Br J Haematol 1994 87: 825–831

    Article  CAS  PubMed  Google Scholar 

  36. Elias AD, Ayash L, Anderson KC et al. 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 79: 3036–3044

    CAS  PubMed  Google Scholar 

  37. Kohno A, Takeyama K, Narabayashi M et al. Low-dose granulocyte colony-stimulating factor enables the efficient collection of peripheral blood stem cells after disease-oriented, conventional-dose chemotherapy for breast cancer, malignant lymphoma and germ cell tumor Bone Marrow Transplant 1995 15: 49–54

    CAS  PubMed  Google Scholar 

  38. Harris JR, Morrow M, Norton L . Malignant tumors of the breast. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer. Principles and Practice of Oncology Lippincott-Raven: Philadelphia 1997 pp 1557–1616

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bone Marrow Transplant Program, University of Connecticut Health Center, Farmington, CT, USA

    S Bilgrami, JM Feingold, RD Bona, RL Edwards, AM Khan, F Rodriguez-Pinero, IA Khan, D Kazierad, J Clive & PJ Tutschka

Authors
  1. S Bilgrami
    View author publications

    Search author on:PubMed Google Scholar

  2. JM Feingold
    View author publications

    Search author on:PubMed Google Scholar

  3. RD Bona
    View author publications

    Search author on:PubMed Google Scholar

  4. RL Edwards
    View author publications

    Search author on:PubMed Google Scholar

  5. AM Khan
    View author publications

    Search author on:PubMed Google Scholar

  6. F Rodriguez-Pinero
    View author publications

    Search author on:PubMed Google Scholar

  7. IA Khan
    View author publications

    Search author on:PubMed Google Scholar

  8. D Kazierad
    View author publications

    Search author on:PubMed Google Scholar

  9. J Clive
    View author publications

    Search author on:PubMed Google Scholar

  10. PJ Tutschka
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bilgrami, S., Feingold, J., Bona, R. et al. Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer. Bone Marrow Transplant 25, 123–130 (2000). https://doi.org/10.1038/sj.bmt.1702125

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702125

Keywords

This article is cited by

Search

Advanced search

Quick links