Abstract
We compared adjuvant chemotherapy-related myocardial damage by antimyosin scintigraphy in patients who received either nine cycles of FEC (fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (group I, n = 14), three cycles of FEC followed by high-dose chemotherapy with alkylating agents (CTCb) given with the support of peripheral blood stem cell transplantation (group II, n = 14), or six cycles of standard intravenous CMF (cyclophosphamide, methotrexate and fluorouracil; group III, n = 8). The cardiac uptake of In-111-antimyosin-Fab (R11D10) antibody was measured and the heart-to-lung ratio (HLR) calculated 8–36 months after the last dose of chemotherapy. Cardiac antimyosin antibody uptake was considerably higher among patients treated with nine cycles of dose-escalated FEC than among those who were treated with three cycles of FEC and high-dose CTCb (HLR, median 1.98; range 1.36–2.24 vs median 1.51; range 1.20–1.82;P< 0.001), or those treated with CMF (median 1.44; range 1.15–1.68;P< 0.001). The difference between groups II and III was not significant (P> 0.1). A linear association was found between the cumulative dose of epirubicin and the cardiac antimyosin uptake (P< 0.001). We conclude that subclinical cardiac damage caused by three cycles of conventional-dose FEC followed by one cycle of high-dose CTCb chemotherapy is small as compared with the damage caused by dose-escalated FEC. © 2000 Cancer Research Campaign
Keywords: breast cancer, chemotherapy, adverse effects, high-dose therapy, epirubicin, antimyosin scintigraphy
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- Antman K. H., Rowlings P. A., Vaughan W. P., Pelz C. J., Fay J. W., Fields K. K., Freytes C. O., Gale R. P., Hillner B. E., Holland H. K. High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America. J Clin Oncol. 1997 May;15(5):1870–1879. doi: 10.1200/JCO.1997.15.5.1870. [DOI] [PubMed] [Google Scholar]
- Astorri E., Contini G. A., Fiorina P., Gavaruzzi G., Fesani F. Myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass surgery. Int J Cardiol. 1996 Aug;55(3):239–244. doi: 10.1016/0167-5273(96)02691-5. [DOI] [PubMed] [Google Scholar]
- Ballester M., Martí V., Carrió I., Obrador D., Moya C., Pons-Lladó G., Bernà L., Lamich R., Aymat M. R., Barbanoj M. Spectrum of alcohol-induced myocardial damage detected by indium-111-labeled monoclonal antimyosin antibodies. J Am Coll Cardiol. 1997 Jan;29(1):160–167. doi: 10.1016/s0735-1097(96)00425-1. [DOI] [PubMed] [Google Scholar]
- Ballester M., Martí V., Obrador D., Carrió I., Marrugat J. Role of 111 In-monoclonal antimyosin antibodies in risk stratification of patients with dilated cardiomyopathy referred for heart transplantation. Transplant Proc. 1997 Feb-Mar;29(1-2):589–591. doi: 10.1016/s0041-1345(96)00316-8. [DOI] [PubMed] [Google Scholar]
- Bengel F. M., Feistel H., Moshage W., Bachmann K., Wolf F. Myocardial damage assessed by indium-111-antimyosin: correlation with persistent enteroviral ribonucleic acid in dilated cardiomyopathy. Eur J Nucl Med. 1997 Sep;24(9):1128–1131. doi: 10.1007/BF01254244. [DOI] [PubMed] [Google Scholar]
- Bergh J., Wiklund T., Erikstein B., Fornander T., Bengtsson N. O., Malmström P., Kellokumpu-Lehtinen P., Anker G., Bennmarker H., Wilking N. Dosage of adjuvant G-CSF (filgrastim)-supported FEC polychemotherapy based on equivalent haematological toxicity in high-risk breast cancer patients. Scandinavian Breast Group, Study SBG 9401. Ann Oncol. 1998 Apr;9(4):403–411. doi: 10.1023/a:1008252014312. [DOI] [PubMed] [Google Scholar]
- Bhattacharya S., Lahiri A. Clinical role of indium-111 antimyosin imaging. Eur J Nucl Med. 1991;18(11):889–895. doi: 10.1007/BF02258455. [DOI] [PubMed] [Google Scholar]
- Booser D. J., Hortobagyi G. N. Anthracycline antibiotics in cancer therapy. Focus on drug resistance. Drugs. 1994 Feb;47(2):223–258. doi: 10.2165/00003495-199447020-00002. [DOI] [PubMed] [Google Scholar]
- Braverman A. C., Antin J. H., Plappert M. T., Cook E. F., Lee R. T. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol. 1991 Jul;9(7):1215–1223. doi: 10.1200/JCO.1991.9.7.1215. [DOI] [PubMed] [Google Scholar]
- Carrió I., Estorch M., Berná L., López-Pousa J., Tabernero J., Torres G. Indium-111-antimyosin and iodine-123-MIBG studies in early assessment of doxorubicin cardiotoxicity. J Nucl Med. 1995 Nov;36(11):2044–2049. [PubMed] [Google Scholar]
- Carrió I., Lopez-Pousa A., Estorch M., Duncker D., Berná L., Torres G., de Andrés L. Detection of doxorubicin cardiotoxicity in patients with sarcomas by indium-111-antimyosin monoclonal antibody studies. J Nucl Med. 1993 Sep;34(9):1503–1507. [PubMed] [Google Scholar]
- Dardir M. D., Ferrans V. J., Mikhael Y. S., el-Grindy M. S., el-Aasar A. B., el-Zawahry H. M., Alling D. W., Banks S. M., el-Mawla N. G. Cardiac morphologic and functional changes induced by epirubicin chemotherapy. J Clin Oncol. 1989 Jul;7(7):947–958. doi: 10.1200/JCO.1989.7.7.947. [DOI] [PubMed] [Google Scholar]
- Estorch M., Carrió I., Martínez-Duncker D., Berná L., Torres G., Alonso C., Ojeda B. Myocyte cell damage after administration of doxorubicin or mitoxantrone in breast cancer patients assessed by indium 111 antimyosin monoclonal antibody studies. J Clin Oncol. 1993 Jul;11(7):1264–1268. doi: 10.1200/JCO.1993.11.7.1264. [DOI] [PubMed] [Google Scholar]
- Fraiser L. H., Kanekal S., Kehrer J. P. Cyclophosphamide toxicity. Characterising and avoiding the problem. Drugs. 1991 Nov;42(5):781–795. doi: 10.2165/00003495-199142050-00005. [DOI] [PubMed] [Google Scholar]
- Goldberg M. A., Antin J. H., Guinan E. C., Rappeport J. M. Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood. 1986 Nov;68(5):1114–1118. [PubMed] [Google Scholar]
- Gratwohl A., Hermans J., Baldomero H. Blood and marrow transplantation activity in Europe 1995. European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 1997 Mar;19(5):407–419. doi: 10.1038/sj.bmt.1700694. [DOI] [PubMed] [Google Scholar]
- Green M. Anthracycline cardiotoxicity, no longer an issue? Ann Oncol. 1998 Jul;9(7):691–693. doi: 10.1023/a:1008347226717. [DOI] [PubMed] [Google Scholar]
- Jain K. K., Casper E. S., Geller N. L., Hakes T. B., Kaufman R. J., Currie V., Schwartz W., Cassidy C., Petroni G. R., Young C. W. A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J Clin Oncol. 1985 Jun;3(6):818–826. doi: 10.1200/JCO.1985.3.6.818. [DOI] [PubMed] [Google Scholar]
- Jensen B. V., Nielsen S. L., Skovsgaard T. Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy. Lancet. 1996 Feb 3;347(8997):297–299. doi: 10.1016/s0140-6736(96)90469-9. [DOI] [PubMed] [Google Scholar]
- Kairemo K. J., Blomqvist C. P., Miettinen M. Cardiac myxomas. N Engl J Med. 1996 May 23;334(21):1407–1409. [PubMed] [Google Scholar]
- Kairemo K. J., Wiklund T. A., Liewendahl K., Miettinen M., Heikkonen J. J., Virkkunen P. J., Aronen H. J., Blomqvist C. P. Imaging of soft-tissue sarcomas with indium-111-labeled monoclonal antimyosin Fab fragments. J Nucl Med. 1990 Jan;31(1):23–31. [PubMed] [Google Scholar]
- Legha S. S., Benjamin R. S., Mackay B., Ewer M., Wallace S., Valdivieso M., Rasmussen S. L., Blumenschein G. R., Freireich E. J. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med. 1982 Feb;96(2):133–139. doi: 10.7326/0003-4819-96-2-133. [DOI] [PubMed] [Google Scholar]
- Lopez M., Vici P., Di Lauro K., Conti F., Paoletti G., Ferraironi A., Sciuto R., Giannarelli D., Maini C. L. Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas. J Clin Oncol. 1998 Jan;16(1):86–92. doi: 10.1200/JCO.1998.16.1.86. [DOI] [PubMed] [Google Scholar]
- Nielsen D., Jensen J. B., Dombernowsky P., Munck O., Fogh J., Brynjolf I., Havsteen H., Hansen M. Epirubicin cardiotoxicity: a study of 135 patients with advanced breast cancer. J Clin Oncol. 1990 Nov;8(11):1806–1810. doi: 10.1200/JCO.1990.8.11.1806. [DOI] [PubMed] [Google Scholar]
- Schütz A., Breuer M., Kemkes B. M. Antimyosin antibodies in cardiac rejection. Ann Thorac Surg. 1997 Feb;63(2):578–581. doi: 10.1016/s0003-4975(96)01106-x. [DOI] [PubMed] [Google Scholar]
- Torti F. M., Bristow M. M., Lum B. L., Carter S. K., Howes A. E., Aston D. A., Brown B. W., Jr, Hannigan J. F., Jr, Meyers F. J., Mitchell E. P. Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy. Cancer Res. 1986 Jul;46(7):3722–3727. [PubMed] [Google Scholar]
- Valdés Olmos R. A., ten Bokkel Huinink W. W., ten Hoeve R. F., van Tinteren H., Bruning P. F., van Vlies B., Hoefnagel C. A. Usefulness of indium-111 antimyosin scintigraphy in confirming myocardial injury in patients with anthracycline-associated left ventricular dysfunction. Ann Oncol. 1994 Sep;5(7):617–622. doi: 10.1093/oxfordjournals.annonc.a058933. [DOI] [PubMed] [Google Scholar]
- Verna E., Ceriani L., Casucci R., Repetto S., Roncari G., Binaghi G. Myocardial uptake of indium-111 antimyosin after coronary angioplasty. Relationship with the total burden of ischaemia. Eur Heart J. 1995 Apr;16(4):478–484. doi: 10.1093/oxfordjournals.eurheartj.a060939. [DOI] [PubMed] [Google Scholar]
- Yamada T., Matsumori A., Watanabe Y., Tamaki N., Yonekura Y., Endo K., Konishi J., Kawai C. Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis. J Am Coll Cardiol. 1990 Nov;16(5):1280–1286. doi: 10.1016/0735-1097(90)90566-8. [DOI] [PubMed] [Google Scholar]
- Yamada T., Tamaki N., Morishima S., Konishi J., Yoshida A., Matsumori A. Time course of myocardial infarction evaluated by indium-111-antimyosin monoclonal antibody scintigraphy: clinical implications and prognostic value. J Nucl Med. 1992 Aug;33(8):1501–1508. [PubMed] [Google Scholar]