Dose Intensification Using High-Dose Combination Alkylating Agents and Autologous Bone Marrow Support in the Treatment of Primary and Metastatic Breast Cancer: A Review of the Duke Bone Marrow Transplantation Program Experience

  • W. P. Peters

Abstract

In 1989, the treatment for metastatic breast cancer is generally considered palliative Despite the availability of more than 15 active agents in the treatment of this disease and the ability to induce objective tumor regressions in 60%–80% of treated patients, few, if any, patients are cured. Since the 1940s, the median survival for patients with metastatic breast cancer has averaged approximately 22 months, with the median time to treatment failure for most combination chemotherapy regimens studied in randomized clinical trials averaging between 5 and 11 months. Complete responses in the treatment of the disease are infrequent. Most therapeutic regimens, even so-called intensive chemotherapy regimens, rarely produce complete responses in excess of 20%. Several single institution trials more recently have reported complete responses in excess of 30% and may represent important new leads in the treament of this disease [1–3]. Nonetheless, the majority of patients fail to achieve complete disease regression, and relapse and progression of their breast cancer is therefore inevitable.

Keywords

Toxicity Lymphoma Leukemia Adenocarcinoma Methotrexate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jones RB, Shpall EJ, Shogan J, Moore J, Gockerman J, Peters WP (1988) AFM induction chemotherapy followed by intensive consolidation with autologous bone marrow (ABM) support for advanced breast cancer. Proc AM Soc Clin Oncol 7: 8Google Scholar
  2. 2.
    Jones RB, Shpall EJ, Peters WP 1987 AFM-intensive induction chemotherapy for advanced breast cancer (Abstract). Breast Cancer Res Treat 10: 90Google Scholar
  3. 3.
    Beveridge RA, Abeloff MD, Donehower RC, Damron DJ, Fetting JH, Waterfield W (1988) Sixteen week dose intense chemotherapy for breast cancer (BC). Proc Am Soc Clin Oncol 7: 13Google Scholar
  4. 4.
    Schabel FM (1975) Animal models as predictive systems. In: Cancer chemotherapy - fundamental concepts and recent advances. Year Book Medical Publishers, Chicago, pp 323–355Google Scholar
  5. 5.
    Skipper HE, Schabel FM Jr (1982) Quantitative and cytokinetic studies in experimental tumor systems. In: Holland JF, Frei EF III (eds) Cancer Medicine. Lea & Febiger, Philadelphia pp 663–685Google Scholar
  6. 6.
    Schabel FM, Griswold DP Jr, Corbett TH et al. (1979) Testing therapeutic hypotheses in mice and man: observations on the therapeutic activity against advanced solid tumors in mice treated with anticancer drugs that have demonstrated or potential cl nical utility for treatment of advanced solid tumors of man. Methods Cancer Res 17: 3–5Google Scholar
  7. 7.
    Griswold DP, Trader MW, Frei EF, Peters WP, Wolpert MK, Laster WR (1987) Response of drug-sensitive and resistant LI210 leukemias to high dose chemotherapy. Cancer Res 47: 2323–2327PubMedGoogle Scholar
  8. 8.
    Peters WP, Eder JP, Henner WD, Schryber S, Wilmore D, Finberg R, Schoenfeld D, Bast R, Antman K, Anderson K, Kruskall MS, Gargone B, Schnipper L, and Frei E III (1986) High dose combination alkylating agents with autologous bone marrow support: a phase I trial. J Clin Oncol 4: 646–654PubMedGoogle Scholar
  9. 9.
    Peters WP, Shpall EJ, Jones RB, Olsen G, Gockerman J, Eder JP, Antman K, Kurtzberg J, Bast RC, Moore JO, Egorin MJ (1987) Critical factors in the design of high-dose combination chemotherapy regimens. In: Herzig TP (ed) Advance in cancer ch emotherapy. Park Row, New York pp 43–52Google Scholar
  10. 10.
    L1210 leukemia; treatment at different stages of advancement with cyclophosphamide delivered in different ways; effects of dose intensity, duration of treatment, and total dose on the surviving leukemia cell burden at the end of treatment, the cure rate, and the survival time of treatment failures. Southern Research Institute, Booklet 11, July 20, 1988.Google Scholar
  11. 11.
    Southern Research Institute (1988) LI210 leukemia; treatment with BCNU delivered in different ways; effects of dose intensity, duration of treatment, and total dose on the degree and duration of therapeutic response (Booklet 12, July 28, 1988 ) Southrn Research Institute Birmingham, ALGoogle Scholar
  12. 12.
    Hryniuk W, Bush H (1984) The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol 2: 1281–1288PubMedGoogle Scholar
  13. 13.
    Hryniuk W, Levine MN (1986) Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol 4: 1162–1170PubMedGoogle Scholar
  14. 14.
    Sykes M, Karnofsky D, Phillips F et al. (1953) Clinical studies of triethylenephos-phoramide and diethylenephosphoramide compounds with nitrogen mustard-like activity. Cancer 6: 142–148CrossRefGoogle Scholar
  15. 15.
    Craig AW, Fox BW, Jackson H (1959) Metabolic studies of 32P-labeled triethylenethiophosphoramide. Biochem Pharmacol 3: 42–50PubMedCrossRefGoogle Scholar
  16. 16.
    Personeus G, Halliday SL, McKenzie D et al. (1952) Effect of a series of ethyleneimine derivatives against metastasizing mammary adenocarcinoma of the rat. proc Soc Exp Biol Med 81: 614–616PubMedGoogle Scholar
  17. 17.
    Peters WP, Shpall EJ, Jones RB, Olsen GA, Gockerman JP, Bast RC, Moore JO (1988) High dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol 6: 1368–1376PubMedGoogle Scholar
  18. 18.
    Peters WP, Jones RB, Shpall EJ, Gockerman JP, Kurtzberg J, Moore JO, Bast RC, Gilbert C, Blackburn B, Coniglio D, Brophy L, and Edwards S (1987) Strategies in the treatment of breast cancer with intensive chemotherapy and autologous bone marrow support. In: Dicke KA, (ed) Autologous bone marrow tansplantation: proceedings of the third international symposium. M.D. Anderson Hospital and Tumor Institute, Houston, Texas 1987 pp 465–474Google Scholar
  19. 19.
    Jones RB, Shpall EJ, Shogan J, Moore J, Gockerman J, Peters WP (1988) AFM induction chemotherapy followed by intensive consolidation with autologous bone marrow (ABM) support for advanced breast cancer. Proc Am Soc Clin Oncol 7: 8Google Scholar
  20. 20.
    Brandt SJ, Peters WP, Atwater SK, Kurtzberg J, Borowitz MJ, Jones RB, Shpall EJ, Gilbert CJ, Bast RC Jr. Oette DH (1988) Effect of recombinant human granulocyte- macrophage colony-stimulating factor on hematopoietic reconstitution following high- dose chemotherapy and autologous bone marrow transplantation. N Engl J Med 318: 869–876PubMedCrossRefGoogle Scholar
  21. 21.
    Peters WP, Kurtzberg J, Atwater S, Borowitz M, Gilbert C, Rao M, Currie M, Shogan J, Jones RB, Shpall EJ, Souza L (1988) Comparative effects of rHuG-CSF and rHuGM- CSF on hematopoietic reconstitution and granulocyte function following high dose chemotherapy and autologous bone marrow transplantation (ABMT). Blood 72 [Suppl 1] 130aGoogle Scholar
  22. 22.
    Peters WP, Kurtzberg J, Atwater S, Borowitz M, Gilbert C, Rao M, Currie M, Shogan J, Jones RB, Shpall EJ, Stead R, and Souza L (1989) Comparative effects of rHuG-CSF and rHuGM-CSF on hematopoietic reconstitution and granulocyte function following high dose chemotherapy and autologous bone marrow transplantation (ABMT). Proc Am Soc Clin Oncol 8: 702Google Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1991

Authors and Affiliations

  • W. P. Peters
    • 1
  1. 1.Duke University Bone Marrow Transplantation ProgramDuke University Medical CenterDurhanUSA

Personalised recommendations