FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 342:1069-1076 April 13, 2000 Number 15 Next

	Full Text PDF Editorial by Lippman, M. E. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background We conducted a randomized trial in which we compared high-dose chemotherapy plus hematopoietic stem-cell rescue with a prolonged course of monthly conventional-dose chemotherapy in women with metastatic breast cancer.

Methods Women 18 to 60 years of age who had metastatic breast cancer received four to six cycles of standard combination chemotherapy. Patients who had a complete or partial response to induction chemotherapy were then randomly assigned to receive either a single course of high doses of carboplatin, thiotepa, and cyclophosphamide plus transplantation of autologous hematopoietic stem cells or up to 24 cycles of cyclophosphamide, methotrexate, and fluorouracil in conventional doses. The primary end point was survival.

Results The median follow-up was 37 months. Of 553 patients who enrolled in the study, 58 had a complete response to induction chemotherapy and 252 had a partial response. Of these, 110 patients were assigned to receive high-dose chemotherapy plus hematopoietic stem cells and 89 were assigned to receive conventional-dose chemotherapy. In an intention-to-treat analysis, we found no significant difference in survival overall at three years between the two treatment groups (32 percent in the transplantation group and 38 percent in the conventional-chemotherapy group). There was no significant difference between the two treatments in the median time to progression of the disease (9.6 months for high-dose chemotherapy plus hematopoietic stem cells and 9.0 months for conventional-dose chemotherapy).

Conclusions As compared with maintenance chemotherapy in conventional doses, high-dose chemotherapy plus autologous stem-cell transplantation soon after the induction of a complete or partial remission with conventional-dose chemotherapy does not improve survival in women with metastatic breast cancer.

Source Information

From the University of Pennsylvania Cancer Center, Philadelphia (E.A.S., C.S., J.H.G.); Dana–Farber Cancer Institute, Boston (A.O.); Fox Chase Cancer Center, Philadelphia (L.J.G.); Hahnemann University, Philadelphia (P.A.C., I.B.); Temple University, Philadelphia (K.F.M.); Mayo Clinic, Rochester, Minn. (J.N.I.); John Wayne Cancer Institute, Santa Monica, Calif. (S.M.); University Hospitals of Cleveland, Cleveland (H.M.L.); and Tufts–New England Medical Center, Boston (J.K.E.). Other authors were Selina M. Luger, M.D., University of Pennsylvania Cancer Center, Philadelphia; Thomas R. Klumpp, M.D., Temple University, Philadelphia; Mark R. Litzow, M.D., Mayo Clinic, Rochester, Minn.; and David L. Topolsky, M.D., Hahnemann University Hospital, Philadelphia.

Address reprint requests to Dr. Stadtmauer at the Bone Marrow and Stem Cell Transplant Program, University of Pennsylvania Cancer Center, 16 Penn Tower, 3400 Spruce St., Philadelphia, PA 19104, or at stadtmau{at}mail.med.upenn.edu.

Full Text of this Article

Related Letters:

High-Dose Chemotherapy plus Hematopoietic Stem-Cell Rescue for Metastatic Breast Cancer
Tempfer C., Seifert M., Brodowicz T., Auerbach L., Zielinski C., Iacopino P., Palazzo S., Patrone F., Stadtmauer E. A., Goldstein L. J., Glick J. H.
Extract | Full Text  
N Engl J Med 2000; 343:439-441, Aug 10, 2000. Correspondence

This article has been cited by other articles:

• Lauer, M. S. (2009). Discarding Logic: 2008 Ancel Keys Memorial Lecture. Circulation 119: 1533-1537 [Full Text]  
• Lazarus, H. M., Phillips, G. L., Herzig, R. H., Hurd, D. D., Wolff, S. N., Herzig, G. P. (2008). High-Dose Melphalan and the Development of Hematopoietic Stem-Cell Transplantation: 25 Years Later. JCO 26: 2240-2243 [Full Text]  
• Leff, B., Finucane, T. E. (2008). Gizmo Idolatry. JAMA 299: 1830-1832 [Full Text]  
• Stadtmauer, E. A. (2008). A Dramatic Story of Hope and Reality. JCO 26: 11-12 [Full Text]  
• Crump, M., Gluck, S., Tu, D., Stewart, D., Levine, M., Kirkbride, P., Dancey, J., O'Reilly, S., Shore, T., Couban, S., Girouard, C., Marlin, S., Shepherd, L., Pritchard, K. I. (2008). Randomized Trial of High-Dose Chemotherapy With Autologous Peripheral-Blood Stem-Cell Support Compared With Standard-Dose Chemotherapy in Women With Metastatic Breast Cancer: NCIC MA.16. JCO 26: 37-43 [Abstract] [Full Text]  
• Jacobson, P. D., Rettig, R. A., Aubry, W. M. (2007). Litigating the Science of Breast Cancer Treatment. Journal of Health Politics, Policy and Law 32: 785-818 [Abstract]  
• Kroger, N., Frick, M., Gluz, O., Mohrmann, S., Metzner, B., Jackisch, C., Ko, Y., Lindemann, H.-W., Meier, C. R., Lohrmann, H. P., Ruffert, U., Hanel, M., Bodenstein, H., Neubauer, A., Ehninger, G., Wolf, H.-H., Kolbe, K., Burock, K., Zander, A. R., Nitz, U. (2006). Randomized Trial of Single Compared With Tandem High-Dose Chemotherapy Followed by Autologous Stem-Cell Transplantation in Patients With Chemotherapy-Sensitive Metastatic Breast Cancer. JCO 24: 3919-3926 [Abstract] [Full Text]  
• Cachin, F., Prince, H. M., Hogg, A., Ware, R. E., Hicks, R. J. (2006). Powerful Prognostic Stratification By [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Metastatic Breast Cancer Treated With High-Dose Chemotherapy. JCO 24: 3026-3031 [Abstract] [Full Text]  
• Mayer, M. (2006). Listen to all the voices: an advocate's perspective on early access to investigational therapies. Clin Trials 3: 149-153 [Abstract]  
• Schrag, D., Samson, D. J., Seidenfeld, J., Aronson, N., Garewal, H., Burstein, H. J., Von Hoff, D. D., Somerfield, M. R. (2005). In Reply:. JCO 23: 3646-3648 [Full Text]  
• Schmid, P., Schippinger, W., Nitsch, T., Huebner, G., Heilmann, V., Schultze, W., Hausmaninger, H., Wischnewsky, M., Possinger, K. (2005). Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial. JCO 23: 432-440 [Abstract] [Full Text]  
• Dhodapkar, M. V., Hussein, M. A., Rasmussen, E., Solomon, A., Larson, R. A., Crowley, J. J., Barlogie, B. (2004). Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628. Blood 104: 3520-3526 [Abstract] [Full Text]  
• Nieto, Y., Vredenburgh, J. J., Shpall, E. J., Bearman, S. I., McSweeney, P. A., Chao, N., Rizzieri, D., Gasparetto, C., Matthes, S., Baron, A. E., Jones, R. B. (2004). Phase II Feasibility and Pharmacokinetic Study of Concurrent Administration of Trastuzumab and High-Dose Chemotherapy in Advanced HER2+ Breast Cancer. Clin. Cancer Res. 10: 7136-7143 [Abstract] [Full Text]  
• Winer, E. P., Berry, D. A., Woolf, S., Duggan, D., Kornblith, A., Harris, L. N., Michaelson, R. A., Kirshner, J. A., Fleming, G. F., Perry, M. C., Graham, M. L., Sharp, S. A., Keresztes, R., Henderson, I. C., Hudis, C., Muss, H., Norton, L. (2004). Failure of Higher-Dose Paclitaxel to Improve Outcome in Patients With Metastatic Breast Cancer: Cancer and Leukemia Group B Trial 9342. JCO 22: 2061-2068 [Abstract] [Full Text]  
• Childs, R. W. (2004). Evolving trends in hematopoietic cell transplantation for solid tumors: tempering enthusiasm with clinical reality. Ann Oncol 15: 543-544 [Full Text]  
• Gratwohl, A., Baldomero, H., Demirer, T., Rosti, G., Dini, G., Ladenstein, R., Urbano-Ispizua, A. (2004). Hematopoetic stem cell transplantation for solid tumors in Europe. Ann Oncol 15: 653-660 [Abstract] [Full Text]  
• van der Hoeven, J. J.M., Krak, N. C., Hoekstra, O. S., Comans, E. F.I., Boom, R. P.A., van Geldere, D., Meijer, S., van der Wall, E., Buter, J., Pinedo, H. M., Teule, G. J.J., Lammertsma, A. A. (2004). 18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography in Staging of Locally Advanced Breast Cancer. JCO 22: 1253-1259 [Abstract] [Full Text]  
• Qureshi, M. A., Girgis, R. E., Dandapantula, H. K., Abrams, J., Soubani, A. O. (2004). Increased Exhaled Nitric Oxide Following Autologous Peripheral Hematopoietic Stem-Cell Transplantation: A Potential Marker of Idiopathic Pneumonia Syndrome. Chest 125: 281-287 [Abstract] [Full Text]  
• Takimoto, C. H., Rowinsky, E. K. (2003). Dose-Intense Paclitaxel: Deja Vu All Over Again?. JCO 21: 2810-2814 [Full Text]  
• Streitberger, K., Friedrich-Rust, M., Bardenheuer, H., Unnebrink, K., Windeler, J., Goldschmidt, H., Egerer, G. (2003). Effect of Acupuncture Compared with Placebo-Acupuncture at P6 as Additional Antiemetic Prophylaxis in High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation: A Randomized Controlled Single-Blind Trial. Clin. Cancer Res. 9: 2538-2544 [Abstract] [Full Text]  
• Sayers, T. J., Brooks, A. D., Koh, C. Y., Ma, W., Seki, N., Raziuddin, A., Blazar, B. R., Zhang, X., Elliott, P. J., Murphy, W. J. (2003). The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP. Blood 102: 303-310 [Abstract] [Full Text]  
• Joffe, S., Weeks, J. C. (2002). Views of American Oncologists About the Purposes of Clinical Trials. JNCI J Natl Cancer Inst 94: 1847-1853 [Abstract] [Full Text]  
• Gratwohl, A., Baldomero, H., Horisberger, B., Schmid, C., Passweg, J., Urbano-Ispizua, A. (2002). Current trends in hematopoietic stem cell transplantation in Europe. Blood 100: 2374-2386 [Abstract] [Full Text]  
• Miura, Y., Thoburn, C. J., Bright, E. C., Chen, W., Nakao, S., Hess, A. D. (2002). Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin 10 and interferon gamma may be critical mediators for the development of autologous GVHD. Blood 100: 2650-2658 [Abstract] [Full Text]  
• Nottage, M., Siu, L. L. (2002). Principles of Clinical Trial Design. JCO 20: 42s-46 [Full Text]  
• Partridge, A. H., Winer, E. P. (2002). Informing Clinical Trial Participants About Study Results. JAMA 288: 363-365 [Full Text]  
• Welch, H G., Mogielnicki, J. (2002). Presumed benefit: lessons from the American experience with marrow transplantation for breast cancer. BMJ 324: 1088-1092 [Full Text]  
• DeFeo-Jones, D., Brady, S. F., Feng, D.-M., Wong, B. K., Bolyar, T., Haskell, K., Kiefer, D. M., Leander, K., McAvoy, E., Lumma, P., Pawluczyk, J. M., Wai, J., Motzel, S. L., Keenan, K., Van Zwieten, M., Lin, J. H., Garsky, V. M., Freidinger, R., Oliff, A., Jones, R. E. (2002). A Prostate-specific Antigen (PSA)-activated Vinblastine Prodrug Selectively Kills PSA-secreting Cells in Vivo. Molecular Cancer Therapeutics 1: 451-459 [Abstract] [Full Text]  
• Huitema, A. D. R., Spaander, M., Mathot, R. A. A., Tibben, M. M., Holtkamp, M. J., Beijnen, J. H., Rodenhuis, S. (2002). Relationship between exposure and toxicity in high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin. Ann Oncol 13: 374-384 [Abstract] [Full Text]  
• Nieto, Y., Nawaz, S., Jones, R. B., Shpall, E. J., Cagnoni, P. J., McSweeney, P. A., Baron, A., Razook, C., Matthes, S., Bearman, S. I. (2002). Prognostic Model for Relapse After High-Dose Chemotherapy With Autologous Stem-Cell Transplantation for Stage IV Oligometastatic Breast Cancer. JCO 20: 707-718 [Abstract] [Full Text]  
• Berry, D. A., Broadwater, G., Klein, J. P., Antman, K., Aisner, J., Bitran, J., Costanza, M., Freytes, C. O., Stadtmauer, E., Gale, R. P., Henderson, I. C., Lazarus, H. M., McCarthy, P. L. Jr, Norton, L., Parnes, H., Pecora, A., Perry, M. C., Rowlings, P., Spitzer, G., Horowitz, M. M. (2002). High-Dose Versus Standard Chemotherapy in Metastatic Breast Cancer: Comparison of Cancer and Leukemia Group B Trials With Data From the Autologous Blood and Marrow Transplant Registry. JCO 20: 743-750 [Abstract] [Full Text]  
• Mello, M. M., Brennan, T. A. (2001). The Controversy Over High-Dose Chemotherapy With Autologous Bone Marrow Transplant For Breast Cancer. Health Aff (Millwood) 20: 101-117 [Abstract] [Full Text]  
• Kobune, M., Xu, Y., Baum, C., Kelley, M. R., Williams, D. A. (2001). Retrovirus-mediated Expression of the Base Excision Repair Proteins, Formamidopyrimidine DNA Glycosylase or Human Oxoguanine DNA Glycosylase, Protects Hematopoietic Cells from N,N',N''-Triethylenethiophosphoramide (thioTEPA)-induced Toxicity in Vitro and in Vivo. Cancer Res. 61: 5116-5125 [Abstract] [Full Text]  
• Kasimir-Bauer, S., Mayer, S., Bojko, P., Borquez, D., Neumann, R., Seeber, S. (2001). Survival of Tumor Cells in Stem Cell Preparations and Bone Marrow of Patients with High-Risk or Metastatic Breast Cancer after Receiving Dose-intensive or High-Dose Chemotherapy. Clin. Cancer Res. 7: 1582-1589 [Abstract] [Full Text]  
• Strother, D., Ashley, D., Kellie, S. J., Patel, A., Jones-Wallace, D., Thompson, S., Heideman, R., Benaim, E., Krance, R., Bowman, L., Gajjar, A. (2001). Feasibility of Four Consecutive High-Dose Chemotherapy Cycles With Stem-Cell Rescue for Patients With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor After Craniospinal Radiotherapy: Results of a Collaborative Study. JCO 19: 2696-2704 [Abstract] [Full Text]  
• Del Mastro, L., Venturini, M., Lionetto, R., Carnino, F., Guarneri, D., Gallo, L., Contu, A., Pronzato, P., Vesentini, L., Bergaglio, M., Comis, S., Rosso, R. (2001). Accelerated-Intensified Cyclophosphamide, Epirubicin, and Fluorouracil (CEF) Compared With Standard CEF in Metastatic Breast Cancer Patients: Results of a Multicenter, Randomized Phase III Study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group. JCO 19: 2213-2221 [Abstract] [Full Text]  
• Morreim, E. H. (2001). From the Clinics to the Courts: The Role Evidence Should Play in Litigating Medical Care. Journal of Health Politics, Policy and Law 26: 409-428  
• Doolittle, N. D., Anderson, C. P., Bleyer, W. A., Cairncross, J. G., Cloughesy, T., Eck, S. L., Guastadisegni, P., Hall, W. A., Muldoon, L. L., Patel, S. J., Peereboom, D., Siegal, T., Neuwelt, E. A., for the Blood-Brain Barrier Disruption Consortium, (2001). Importance of dose intensity in neurooncology clinical trials: Summary Report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium. Neuro Oncol Duke 3: 46-54 [Abstract]  
• Ozer, H., Armitage, J. O., Bennett, C. L., Crawford, J., Demetri, G. D., Pizzo, P. A., Schiffer, C. A., Smith, T. J., Somlo, G., Wade, J. C., Wade, J. L. III, Winn, R. J., Wozniak, A. J., Somerfield, M. R., for the American Society of Clinical Oncology Gro, (2000). 2000 Update of Recommendations for the Use of Hematopoietic Colony-Stimulating Factors: Evidence-Based, Clinical Practice Guidelines. JCO 18: 3558-3585 [Full Text]  
• Rodenhuis, S. (2000). The Status of High-Dose Chemotherapy in Breast Cancer. The Oncologist 5: 369-375 [Abstract] [Full Text]  
• Kamen, B. A., Rubin, E., Aisner, J., Glatstein, E. (2000). High-Time Chemotherapy or High Time for Low Dose. JCO 18: 2935-2937 [Full Text]  
• Vickers, A., Christos, P. (2000). Bezwoda: Evidence of Fabrication in Original Article. JCO 18: 2933-2933 [Full Text]  
• Tempfer, C., Seifert, M., Brodowicz, T., Auerbach, L., Zielinski, C., Iacopino, P., Palazzo, S., Patrone, F., Stadtmauer, E. A., Goldstein, L. J., Glick, J. H. (2000). High-Dose Chemotherapy plus Hematopoietic Stem-Cell Rescue for Metastatic Breast Cancer. NEJM 343: 439-441 [Full Text]  
• Canellos, G. P. (2000). The Policing of Clinical Trials. JCO 18: 2353-2353 [Full Text]  
• Morreim, E. H. (2000). Quality of Life: Erosions and Opportunities Under Managed Care. J Law Med Ethics 28: 144-158  
• (2000). High-Dose Chemo for Breast Cancer: Disappointing News. Journal Watch Dermatology 2000: 15-15 [Full Text]  
• (2000). Stem-Cell Transplantation Does Not Improve Survival in Metastatic Breast Cancer. JWatch Women's Health 2000: 1-1 [Full Text]  
• (2000). Disappointing News About Stem-Cell-Supported High-Dose Chemotherapy for Breast Cancer. JWatch General 2000: 1-1 [Full Text]  
• Lippman, M. E. (2000). High-Dose Chemotherapy plus Autologous Bone Marrow Transplantation for Metastatic Breast Cancer. NEJM 342: 1119-1120 [Full Text]