Abstract
Breast cancer patients with cardiac disease are usually excluded from clinical trials of high-dose chemotherapy. We treated 52 patients with inflammatory and/or metastatic disease with sequential high-dose melphalan and stem cell rescue followed by high-dose thiotepa and stem cell rescue. Stem cells were mobilized with cyclophosphamide and/or paclitaxel and filgrastim. Left ventricular ejection fraction (LVEF) was measured by equilibrium radionuclide angiocardiography (ERNA) at baseline, after each course of chemotherapy and 4 weeks after completing both transplants. The mean absolute decrease in LVEF after the two transplants was 3.6% (P = 0.008 for the comparison with baseline LVEF), and most of this drop (−2.5%, P = 0.007) occurred after mobilization. Unexpectedly, paclitaxel was associated with a mean absolute decrease in LVEF of 3.4% (P = 0.032, n = 19), cyclophosphamide alone was not associated with a significant change in LVEF (−1.3%, P = 0.23), but mobilization with sequential paclitaxel and cyclophosphamide resulted in a mean absolute drop of 4.9% in LVEF (P = 0.009). Twelve patients were found to have a reduced LVEF (<50%) at least once during treatment and had a mean absolute decrease in lvef of 10% (P = 0.008) from baseline, compared with a drop of only 1.8% (P = 0.176) in the patients without impaired LV function. Although two of these 12 patients developed symptomatic heart failure, their cardiac symptoms were easily treated and there were no cardiac deaths. We conclude that our protocol has acceptable cardiac toxicity and breast cancer patients with impaired LV function should not be denied high-dose chemotherapy if otherwise indicated. Bone Marrow Transplantation (2000) 26, 133–139.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Von Hoff DD, Layard MW, Basa P et al. Risk factors for doxorubicin-induced congestive heart failure Ann Intern Med 1979 91: 710–717
Singal PK, Iliskovic N . Doxorubicin-induced cardiomyopathy New Engl J Med 1999 339: 900–905
Shan K, Lincoff AM, Young JB . Anthracycline-induced cardiotoxicity Ann Intern Med 1996 125: 47–58
Lipshultz SE, Colan SD, Gelber RD et al. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood New Engl J Med 1991 324: 808–815
Steinherz LJ, Steinherz PG, Tan C . Cardiac failure and dysrhythmias 6–19 years after anthracycline therapy: a series of 15 patients Med Ped Oncology 1995 24: 352–361
Fraiser LH, Kanekal S, Kehrer J . Cyclophosphamide toxicity. Characterising and avoiding the problem Drugs 1991 42: 781–795
Gottdiener JS, Appelbaum FR, Ferrans VJ et al. Cardiotoxicity associated with high-dose cyclophosphamide therapy Arch Intern Med 1981 141: 758–763
Braverman AC, Antin JH, Plapert MT et al. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens J Clin Oncol 1991 9: 1215–1223
Lee C-K, Harman GS, Hohl RJ, Gingrich RD . Fatal cyclophosphamide cardiomyopathy; its clinical course and treatment Bone Marrow Transplant 1996 18: 573–577
Goldberg MA, Antin JH, Guinan EC et al. Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor Blood 1986 68: 1114–1118
Rowinsky EK, McGuire WP, Guarnieri T et al. Cardiac disturbances during the administration of Taxol J Clin Oncol 1991 9: 1704–1712
Garcia-Carbonero R, Hidalgo M, Paz-Ares L et al. Patient selection in high-dose chemotherapy trials: relevance in high-risk breast cancer J Clin Oncol 1997 15: 3178–3184
Burtness BA, Psyrri A, Rose M et al. A phase I study of paclitaxel for mobilization of stem cells Bone Marrow Transplant 1999 23: 311–315
Lee FA, Fetterman R, Zaret BL, Wackers FJTh . Rapid radionuclide-derived systolic and diastolic cardiac function using cycle-dependent background correction and Fourier analysis Computers Cardiol 1986 443–446
van Royen N, Jaffe CC, Krumholz HM et al. Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions Am J Cardiol 1996 77: 843–850
To LB, Haylock DN, Simmons PJ, Juttner CA . The biology and clinical uses of blood stem cells Blood 1997 89: 2233–2258
Basser RL, Abraham R, Bik To L et al. Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer Ann Oncol 1999 10: 53–58
de Graaf H, Dolsma WV, Willemse PHB et al. Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer Br J Cancer 1997 76: 943–945
Carlson K, Smedmyr B, Backlund L, Simonsson B . Subclinical disturbances in cardiac function at rest and in gas exchange during exercise are common findings after autologous bone marrow transplant Bone Marrow Transplant 1994 14: 949–954
Kakavas PW, Ghalie R, Parrillo JE et al. Angiotensin converting enzyme inhibitors in bone marrow transplant recipients with depressed left ventricular function Bone Marrow Transplant 1995 15: 859–861
Ghielmini M, Zappa F, Menafoglio A et al. The high-dose sequential (Milan) chemotherapy/PBSC transplantation regimen for patients with lymphoma is not cardiotoxic Ann Oncol 1999 10: 533–537
Shek TW, Luk IS, Ma L et al. Paclitaxel-induced cardiotoxicity. An ultrastructural study Arch Pathol Lab Med 1996 120: 89–91
Gianni L, Munzone 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: 2688–2699
Sparano JA . Use of dexrazoxane and other strategies to prevent cardiomyopathy associated with doxorubicin-taxane combinations Semin Oncol 1998 25: (4 Suppl. 10) 66–71
Alexander J, Dainiak N, Berger HJ et al. Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography New Engl J Med 1979 300: 278–283
Schwartz RG, McKenzie WB, Alexander J et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography Am J Med 1987 82: 1109–1118
Ganz WI, Sridhar KS, Ganz SS et al. Review of tests for monitoring doxorubicin-induced cardiomyopathy Oncology 1996 53: 461–470
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rose, M., Lee, F., Gollerkeri, A. et al. The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function. Bone Marrow Transplant 26, 133–139 (2000). https://doi.org/10.1038/sj.bmt.1702449
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702449
Keywords
This article is cited by
-
Intrapericardial procedures for cardiac regeneration by stem cells
Herz (2010)
-
Cardiac toxicity of high-dose chemotherapy
Bone Marrow Transplantation (2005)
-
High-dose consolidation chemotherapy with Idarubicin and alkylating agents following induction with gemcitabine–epirubicin–paclitaxel in metastatic breast cancer: a dose finding study
Bone Marrow Transplantation (2003)