Skip to main content
SpringerLink
Log in

Cardioprotection with ICRF-187 (Cardioxane) in patients with advanced breast cancer having cardiac risk factors for doxorubicin cardiotoxicity, treated with the FDC regimen

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

A study of cardioprotection with ICRF-187 (Cardioxane, Eurocetus) has been performed in 35 patients with metastatic breast cancer treated with the FDC regimen (5-fluorouracil 500 mg/m2 i.v., day 1; doxorubicin 50 mg/m2 i.v., day 1; cyclophosphamide 500 mg/ m2 i.v., day 1). All patients had one or more cardiac risk factors for doxorubicin cardiotoxicity including 24 who had previously received left-chest-wall irradiation. Cardioxane was applied at a dosage of 1000 mg/m2 as a 15-min infusion in Ringer lactate solution 30 min before doxorubicin administration. Cardiological monitoring included left-ventricular ejection fraction (LVEF) determination by echocardiography before treatment and before each cycle following the cumulative doxorubicin dose of 200 mg/m2. Of the 35 patients, 34 were evaluable for response, and the overall response rate was 19/34 (56%) with 3/34 complete responses and 16/34 partial responses. Statistical analysis of LVEF values in relation to increasing cumulative doxorubicin doses with Wilcoxon's test of equivalent pairs and Friedman's test has demonstrated that no cardiotoxicity was detected up to a cumulative doxorubicin dose of between 800 mg/m2 and 1000 mg/m2, except for 2 patients in whom a decrease of 20% in relation to the LVEF pretreatment level was demonstrated following a cumulative drug dose of 250 mg/m2. Thus Cardioxane provides an effective cardio-protection even in breast cancer patients with cardiac risk factors for doxorubicin cardiotoxicity treated with the FDC regimen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Basser RL, Green MD (1993) Strategies for prevention of anthracycline cardiotoxicity. Cancer Treat Rev 19:57–77

    Google Scholar 

  2. Billingham ME, Mason GW, Bristow MR, Daniels JR (1978) Anthracycline cardiomyopathy monitored by morphological changes. Cancer Treat Rep 62:865–872

    Google Scholar 

  3. Buzdar AU, Marcus C, Smith TL, Blumenschein GR (1985) Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 55:2761–2765

    Google Scholar 

  4. Chlebowski RT, Paroly WS, Pugh WS, Hueser J, Jacobs EM, Pajak TF, Bateman JR (1980) Adriamycin given as a weekly schedule without a loading course: clinically effective with reduced incidence of cardiotoxicity. Cancer Treat Rep 64:47–51

    Google Scholar 

  5. Demant EJ (1984) Binding of Adriamycine-Fe3+ complex to membrane phospholipids. Eur J Biochem 142:571–575

    Google Scholar 

  6. Demant EJ (1984) Transfer of ferritin-bound iron to Adriamycin. FEBS Lett 176:97–100

    Google Scholar 

  7. Doroshow JH, Locker GY, Baldinger J, Myers CE (1979) The effect of doxorubicin on hepatic and cardiac glutathione. Res Commun Chem Pathol Pharmacol 26:285–295

    Google Scholar 

  8. Doroshow JH, Locker GY, Myers CE (1980) Enzymatic defenses of the mouse heart against reactive oxygen metabolites. J Clin Invest 65:128–135

    Google Scholar 

  9. Feldman SE, Jones SR, Weisburg DR, Gandara DR, Lyman GH, York RM, Mailliard JA, Hayes DM, Tranum B, Spaulding MB, Shaikh BS, Khojasteh A, Wajima T, Rivers RR, Abramson N, Horvath WL, Pendegrass KB, Reynolds RD, Gerber M, Winston J, Squillace K, Kline A, Swearengin B, Hess D, Scott D, Banks P, Jones G, Jones D, Gams RA (1992) Advanced small cell lung cancer treated with CAV chemotherapy and the cardioprotective agent dexrazoxane (ADR-529, ICRF-187, Zinecard). Proc Am Soc Clin Oncol Annu Meet 11:296

    Google Scholar 

  10. Freter CE, Lee TC, Billingham ME, Chak L, Bristow MR (1986) Doxorobicin cardic toxicity manifesting seven years after treatment. Am J Med 80:483–485

    Google Scholar 

  11. Gercovich FG, Rivarolo EG, Rargeneld EL, Mendez-Kitar JM, Pirolo C (1987) Cardiac monitoring of Adriamycin treated patients; influence of risk factors on subclinical cardiotoxicity. Proc Am Soc Clin Oncol Annu Meet 6:A-79

    Google Scholar 

  12. Grannai L, Vigano L, Lanzi C, Niggeler M, Malatesta V (1980) Rote of daunosamine and hydroxy acetyl side chain in reaction with iron and lipid peroxidation. J Natl Cancer Inst 30:1104–1111

    Google Scholar 

  13. Granni L, Zweier L, Levy A, Myers CE (1985) Characterization of the cycle of iron-mediated electron transfer from adriamycin to molecular oxygen. J Biol Chem 260:6820–6826

    Google Scholar 

  14. Gordiener J, Rarhisen DJ, Boter JS, Bonow RO, Myers CE, Born LH, Schartz DE, Bocharach SL, Green MV, Rosenberg S (1981) Doxorubicin cardiotoxicity: assessement of left ventricular dysfunction by radionuclide eineangiography. Ann Intern Vied 94:430–435

    Google Scholar 

  15. Haq MM, Legha SS, Choksi J, Hortobagyi GN, Benjamin RS, Ewer M, Ali A (1985) Doxorubicin-induced congestive heart failure in adults. Cancer 56:1361–1365

    Google Scholar 

  16. Hassinoff BB (1989) The interaction of the cardioprotective agent ICRF-187, its hydrolysis product (ICRF-198) and other chelating agents with Fe(III) and Cu(II) complexes of Adriamycin. Agents Actions 26:378–395

    Google Scholar 

  17. Herman E, Ardalan B, Bier C, Waravdekar V, Krop S (1979) Reduction of dannorubicin lethality and myocardial cellular alterations by pretreatment with ICRF-187 in Syrian golden hamster. Cancer Treat Rep 63:89–92

    Google Scholar 

  18. Hortobagyi GN, Frye D, Buzdar AU, Ewer MS, Fraschini G, Hug V, Ames F, Monague E, Carrasco CH, Mackay B, Benjamia RS (1989) Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast cancer. Cancer 63:37–45

    Google Scholar 

  19. Milles AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214

    Google Scholar 

  20. Minow RA, Benjamin RS, Gottlieb JA (1975) Adriamycin cardiomyopathy—an overview with determination of risk factors. Cancer Chemother Rep 6:195–201

    Google Scholar 

  21. Praga C, Beretta G, Vigo PL (1979) Adriamycin cardiotoxicity: a survey of 1273 patients. Cancer Treat Rep 62:931–934

    Google Scholar 

  22. Speyer J, Green MD, Zeleniuch-Jacquotte A, Wernz JC, Rey M, Sanger J, Kramer E, Ferrans V, Hoschter H, Meyers M, Blum RH, Feit F, Attubato M, Burrows W, Muggia F (1992) ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol 10:117–127

    Google Scholar 

  23. Sugioka K, Nakano H, Nakano M, Tero-Kybota S, Ikegami Y (1983) Generation of hydroxyl radicals during the enzymatic reductions of the FE3+-ADP-phosphate-Adriantycin and FE3+-ADP-EDTA systems. Biochim Biophys Acta 753:411–421

    Google Scholar 

  24. Ten Bokkel Huiniuk WW, Schreuder JE, Dubbleman R, Bierhorst F, Tintern H van, Dalesio O, Valdes Olmos RA, McVic JG (1992) ICRF-187 protects against doxorubicin induced cardiomyopathy. Ann Oncol 3 [Suppl 3]: 114

    Google Scholar 

  25. Van Hoff DD, Layard MW, Basa P, Davis HL, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717

    Google Scholar 

  26. Weisberg SR, Rosenfeld CS, York RM, Jones SE, Spicer DV, Khotajesh A, Desai AM, Wadler S, Mittleman A, Pendergrass KB, Velez-Garcie E, Moore JO, Abramson N, Vogel CL, Swain SM, Lyman GH, Feldman JE, Tranum BL, Lusch CJ, Joseph RR, Banks PLC, Jones D, Squillace K, Winston J, Scott D, Kline A, Hess DL, Heanebert B, Curtis N, Reynolds RD, Imondi A, Filppi J, Narang PK, Palepu N, Verhoef V, Bianchine J, Gans JA (1992) Dextrazoxane (ADR-529, ICRF-187, Zinecard) protects against doxorubicin induced chronic cardiotoxicity. Proc Am Soc Clin Oneo 11:91

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut za Onkologiju i Radiologiju, Pasterova 14, 11000, Belgrade, Yugoslavia

    Svetislav Jelić, Siniša Radulović, Zora Nešković-Konstantinović, Miroslav Kreačić, Zorana Ristović, Snežana Bošnjak, Nenad Milanovic & Labuda Vuletić

Authors
  1. Svetislav Jelić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siniša Radulović
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zora Nešković-Konstantinović
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miroslav Kreačić
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zorana Ristović
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Snežana Bošnjak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nenad Milanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Labuda Vuletić
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jelić, S., Radulović, S., Nešković-Konstantinović, Z. et al. Cardioprotection with ICRF-187 (Cardioxane) in patients with advanced breast cancer having cardiac risk factors for doxorubicin cardiotoxicity, treated with the FDC regimen. Support Care Cancer 3, 176–182 (1995). https://doi.org/10.1007/BF00368887

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00368887

Key words

Search

Navigation