Drugs & Aging

, Volume 19, Issue 7, pp 475–485 | Cite as

High-Dose Chemotherapy and Stem Cell Support for Breast Cancer

Where Are We Now?
  • Renee M. Gerrero
  • Steven Stein
  • Edward A. Stadtmauer
Leading Article

Abstract

To date, there is no definitive evidence that high-dose chemotherapy and haematopoietic stem cell support offers a survival advantage over conventional-dose chemotherapy for metastatic or high-risk primary breast cancer. Studies of metastatic disease discussed in this review have an adequate duration of follow-up given the short natural history of metastatic breast cancer. Thus, the results of these studies are unlikely to change with a longer observation period. On the other hand, studies of high-dose chemotherapy in the treatment of high-risk primary breast cancer need longer follow-up in light of the longer natural history of this type of disease. Results of unpublished studies and longer follow-up of available studies may still demonstrate a survival advantage for high-dose chemotherapy in patients with metastatic or high-risk primary breast cancer. We continue to encourage participation in innovative clinical studies.

Keywords

Breast Cancer Metastatic Breast Cancer Induction Chemotherapy Acute Myeloid Leukaemia Autologous Bone Marrow Transplantation 

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

References

  1. 1.
    Landis SH, Murray T, Bolden S. Cancer Statistics: 1999. CA Cancer J Clin 1999; 49(1): 8–31, 1PubMedCrossRefGoogle Scholar
  2. 2.
    Henderson IC. Basic principles in the use of adjuvant therapy. Semin Oncol 1990; 17: 40–4PubMedGoogle Scholar
  3. 3.
    Berry D, Demetri G, Cirrincione C, et al. Improved disease-free (DFS) and overall survival (OS) from the addition of sequential paclitaxel (T) but not from the escalation of doxorubicin (A) dose level in the adjuvant chemotherapy of patients (PTS) with node-positive primary breast cancer (BC) [abstract]. Proc Am Soc Clin Oncol 1998; 17: 101Google Scholar
  4. 4.
    Fisher B, Anderson S, Wickerham DL, et al. Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from national surgical adjuvant breast and bowel project B-22. J Clin Oncol 1997; 15: 1858–69PubMedGoogle Scholar
  5. 5.
    Greenberg PA, Hortobagyi GN, Smith TL, et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996; 14: 2197–205PubMedGoogle Scholar
  6. 6.
    Sparano JA, O’Neill A, Schaeffer PL, et al. Phase II trial of doxorubicin and docetaxel plus granulocyte colony stimulating factor in metastatic breast cancer: Eastern Cooperative Oncology Group study E1 196. J Clin Oncol 2000; 18: 2369–77PubMedGoogle Scholar
  7. 7.
    Gianni L, Muzone E, Capri G, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 1995; 13: 2688–99PubMedGoogle Scholar
  8. 8.
    Vogel CL, Azevedo S, Hilsenbeck S, et al. Survival after first recurrence of breast cancer. The Miami experience. Cancer 1992; 70(1): 129–35PubMedCrossRefGoogle Scholar
  9. 9.
    Peters WP, Shpall EJ, Jones RB, et al. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol 1988; 6: 1368–76PubMedGoogle Scholar
  10. 10.
    Williams SF, Mick R, Dresser R, et al. High dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer. J Clin Oncol 1989; 7: 1824–30PubMedGoogle Scholar
  11. 11.
    Jones RB, Shpall EJ, Shogan J, et al. The Duke AFM Program. Intensive induction chemotherapy for metastatic breast cancer. Cancer 1990; 66: 431–6PubMedCrossRefGoogle Scholar
  12. 12.
    Antman K, Ayash L, Elias A, et al. A phase II study of high dose cyclophosphamide, thiotepa and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy. J Clin Oncol 1992; 10: 102–10PubMedGoogle Scholar
  13. 13.
    Williams SF, Gilewski T, Mick R, et al. High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer: follow-up report. J Clin Oncol 1992; 10: 1743–7PubMedGoogle Scholar
  14. 14.
    Moonneier JA, Williams SF, Kamminer LS, et al. High dose trialkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies. J Natl Cancer Inst 1990; 82: 29–34CrossRefGoogle Scholar
  15. 15.
    Kennedy MJ, Beveridge RA, Rowley SD, et al. High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose intense induction as initial therapy for metastatic breast cancer. J Natl Cancer Inst. 1991; 83: 920–6PubMedCrossRefGoogle Scholar
  16. 16.
    Eddy DM. High-dose chemotherapy with autologous bone marrow transplantation for the treatment of metastatic breast cancer [review article]. J Clin Oncol 1992; 10: 657–70PubMedGoogle Scholar
  17. 17.
    Klumpp TR, Mangan KF, Glenn LD. Phase II pilot study of high-dose busulfan and CY followed by autologous BM or peripheral blood stem cell transplantation in patients with advanced chemosensitive breast cancer. Bone Marrow Transplant 1993; 11: 337–9PubMedGoogle Scholar
  18. 18.
    Lazarus HM, Gray R, Ciobanu N, et al. A phase I trial of high-dose etoposide and autologous bone marrow reinfusion in solid tumors: An Eastern Cooperative Oncology Group (ECOG) study. Bone Marrow Transplant 1994; 14: 443–8PubMedGoogle Scholar
  19. 19.
    Weaver CH, Bensinger WI, Appelbaum FR, et al. Phase I study of high-dose busulfan, melphalan, and thiotepa with autologous stem cell support in patients with refractory malignancies. Bone Marrow Transplant 1994; 14: 813–9PubMedGoogle Scholar
  20. 20.
    Vaughan WP, Reed EC, Edwards B, et al. High-dose cyclophosphamide, thiotepa and hydroxyurea with autologous hematopoietic stem cell rescue: an effective consolidation chemotherapy regimen for early metastatic breast cancer. Bone Marrow Transplant 1994; 13: 619–24PubMedGoogle Scholar
  21. 21.
    Fields KK, Elfenbein GJ, Lazarus HM, et al. Maximum tolerated doses of ifosfamide, carboplatin and etoposide given over six days followed by autologous stem cell rescue: toxicity profile. J Clin Oncol 1995; 13: 323–32PubMedGoogle Scholar
  22. 22.
    Spitzer TR, Cirenza E, McAfee S, et al. Phase I–II trial of high-dose cyclophosphamide, carboplatin and autologous bone marrow or peripheral blood stem cell rescue. Bone Marrow Transplant 1995; 15: 527–42Google Scholar
  23. 23.
    Gisselbrecht C, Extra JM, Lotz JP, et al. Cyclophosph-amide/mitoxantrone/melphalan (CMA) regimen prior to autologous bone marrow transplantation (ABMT) in metastatic breast cancer. Bone Marrow Transplant 1996; 18: 857–63PubMedGoogle Scholar
  24. 24.
    Stemmer SM, Cagone PJ, Shpall EJ, et al. High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial. J Clin Oncol 1996; 14: 1463–72PubMedGoogle Scholar
  25. 25.
    ABMTR Newsletter 1998; 5: 5Google Scholar
  26. 26.
    Bezwoda W, Seymore L, Dansey R. High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial. J Clin Oncol 1995; 13: 2483–9PubMedGoogle Scholar
  27. 27.
    Bezwoda WR. Randomized, controlled trial of high dose chemotherapy (HD-CNV) versus standard dose (CAF) chemotherapy for high risk, surgically treated, primary breast cancer [abstract]. Proc Am Soc Clin Oncol 1999; 18: 2aGoogle Scholar
  28. 28.
    Stadtmauer EA, O’Neill A, Goldstein LJ, et al. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med 2000; 342(18): 1069–76PubMedCrossRefGoogle Scholar
  29. 29.
    Lotz JP, Cure H, Janvier M, et al. High-dose chemotherapy with hematopoietic stem cells transplantation for metastatic breast cancer: results of the French protocol PEGASE 04 [abstract]. Proc Am Soc Clin Oncol 1999; 18: 43aGoogle Scholar
  30. 30.
    Peters WP, Jones RB, Vredenburg J, et al. A large, prospective, randomized trial of high-dose combination alkylating agents (CBP) with autologous cellular support (ABMS) as consolidation for patients with metastatic breast cancer achieving complete remission after intensive doxorubicin-based induction therapy (AFM) [abstract]. Proc Am Soc Clin Oncol 1996; 15: 121Google Scholar
  31. 31.
    Madan B, Broadwater G, Rubin P, et al. Improved survival with consolidation high dose cyclophosphamide, cisplatin and carmustine (HD-CPB) compared with observation in women with metastatic breast cancer (MBC) and only bone metastasis treated with induction adriamycin, 5-fluorouracil and methotrexate (AFM): a phase III prospective randomized comparative trial [abstract]. Proc Am Soc Clin Oncol 2000; 19: 48aGoogle Scholar
  32. 32.
    Daly MB, Goldstein LJ, Topolsky D, et al. Quality of life experience in women randomized to high-dose chemotherapy (HDC) and stem cell support (SCT) or standard dose chemotherapy for responding metastatic breast cancer in Philadelphia Intergroup Study (PBT-1) [abstract]. Proc Am Soc Clin Oncol 2000; 19: 327Google Scholar
  33. 33.
    Schulman KA, Glick HA, Goldstein LJ, et al. Economic analysis of high-dose chemotherapy for women with responding metastatic breast cancer in the Philadelphia Intergroup Study (PBT-1) [abstract]. Proc Am Soc Clin Oncol 2000; 19: 325Google Scholar
  34. 34.
    Nieto Y, Champlin RE, Wingard JR, et al. Status of high-dose chemotherapy for breast cancer: a review. Biol Blood Marrow Transplant 2000; 6: 476–95PubMedCrossRefGoogle Scholar
  35. 35.
    Peters WP, Ross M, Vredenburgh JJ, et al. High-dose chemotherapy and autologous bone marrow transplant support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. J Clin Oncol 1993; 11: 1132–43PubMedGoogle Scholar
  36. 36.
    Rodenhuis S, Richel DJ, Van der Wall E, et al. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 1998; 352(9127): 515–21PubMedCrossRefGoogle Scholar
  37. 37.
    Rodenhuis S, Botenbal M, Beex LVAM, et al. Randomized phase III study of high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin in operable breast cancer with 4 or more axillary lymph nodes [abstract]. Proc Am Soc Clin Oncol 2000; 19: 74Google Scholar
  38. 38.
    Hortobagyi GN, Buzdar AU, Theriault RL, et al. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst 2000; 92: 225PubMedCrossRefGoogle Scholar
  39. 39.
    Berg J, Wiklund T, Erikstein B, et al. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomized trial. Lancet. 2000; 356: 1384CrossRefGoogle Scholar
  40. 40.
    Peters W, Rosner G, Vredenburgh J, et al. A prospective, randomized comparison of two doses of combination alkylating agents (AA) as consolidation after CAF in high-risk primary breast cancer involving ten or more axillary lymph nodes (LN): preliminary results of CALGB 9082/SWOG 9114/NCIC MA-13 [abstract]. Proc Am Soc Clin Oncol 1999; 18: 1Google Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Renee M. Gerrero
    • 1
  • Steven Stein
    • 1
  • Edward A. Stadtmauer
    • 1
  1. 1.Bone Marrow and Stem Cell Transplant ProgramUniversity of Pennsylvania Cancer CenterPhiladelphiaUSA

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