Breast Cancer Research and Treatment

, Volume 29, Issue 3, pp 271–277 | Cite as

Results of chemotherapy using ifosfamide with doxorubicin in advanced breast cancer

  • Michael Millward
  • Michael Lind
  • Lindsey Gumbrell
  • Angela Robinson
  • Thomas Lennard
  • Brian Cantwell


Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.

Key words

breast cancer doxorubicin chemotherapy ifosfamide 


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  1. 1.
    Goldin A: Ifosfamide in experimental tumor systems. Semin Oncol 4: 14–23, 1982Google Scholar
  2. 2.
    Zalapski M, Baker LH: Ifosfamide. J Natl Cancer Inst 80: 556–566, 1988Google Scholar
  3. 3.
    Markman M, Hakes T, Reichman B, Lewis JL, Rubin S, Jones W, Alamadrones L, Pizzuto F, Hoskins W: Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease. J Clin Oncol 10: 243–248, 1992Google Scholar
  4. 4.
    Hortobagyi GH: Activity of ifosfamide in breast cancer. Semin Oncol 19 (suppl 12): 36–42, 1991Google Scholar
  5. 5.
    Lind MJ, McGowan AT, Hadfield JA, Thatcher N, Crowther D, Fox BW: The effect of ifosfamide and its metabolites on intracellular glutathione levelsin vitro andin vivo. Biochem Pharmacol 38: 1835–1840, 1989Google Scholar
  6. 6.
    Dusre L, Mimnaugh EG, Myers CE: Potentiation of doxorubicin cytotoxicity by buthionine sulfoximine in multidrugresistant human breast tumour cells. Cancer Res 49: 511–515, 1989Google Scholar
  7. 7.
    Millward MJ, Harris AL, Cantwell BMJ: Phase II study of doxorubicin plus ifosfamide/mesna in patients with advanced breast cancer. Cancer 65: 2421–2425, 1990Google Scholar
  8. 8.
    World Health Organisation. Handbook for reporting results of cancer treatment. World Health Organisation, offset publication 48Google Scholar
  9. 9.
    Goldhirsch A, Gelber RD, Castaglione M: Relapse of breast cancer after adjuvant treatment in premenopausal women: patterns and prognoses. J Clin Oncol 6: 89–97, 1988Google Scholar
  10. 10.
    Sainsbury JRC, Farndon JR, Needham GK, Malcolm AJ, Harris AL: Epidermal growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 329: 1398–1402, 1987Google Scholar
  11. 11.
    Cerny T, Kupfer A: The enigma of ifosfamide encephalopathy. Ann Oncol 3: 679–681, 1992Google Scholar
  12. 12.
    Cantwell BMJ, Idle M, Millward MJ, Hall G, Lind MJ: Encephalopathy due to hyponatraemia and inappropriate arginine vasopressin secretion following an intravenous ifosfamide infusion. Ann Oncol 1: 232, 1990Google Scholar
  13. 13.
    Gad-El-Mawla N, Hamza MR, Zikri ZK, Elserafi M, El-Khodari A, Khaled H, Gafaar R: Ifosfamide, methotrexate, and 5-fluorouracil: effective combination in resistant breast cancer. Cancer Chemother Pharmacol 26 (suppl): S85-S86, 1990Google Scholar
  14. 14.
    Becher R, Hofeler H, Kloke O, May D, Wandl U, Niederle N, Richter R, Scheulen ME, Schmidt CG: Ifosfamide, methotrexate, and 5-fluorouracil in advanced pretreated breast cancer. Semin Oncol 16 (suppl 3): 56–59, 1989Google Scholar
  15. 15.
    Bellmunt J, Morales S, Navarro M, Sole L-A: Ifosfamide + mitoxantrone in advanced breast cancer previously treated with anthracyclines. Cancer Chemother Pharmacol 26 (suppl): S81-S84, 1990Google Scholar
  16. 16.
    Perez JE, Machivelli M, Leone BA, Romero A, Rabinovich MG, Vallejo CT, Bianco A, Lacava JA, Rodriguez R, Paris A, Romero Acuna L, Langhi M, Lorusso V, De Lena M: Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer. J Clin Oncol 11: 461–466, 1992Google Scholar
  17. 17.
    Manegold C, Worst P, Bickel J, Schmid H, Drings P, Kaufmann M: Ifosfamide/etoposide and mesna uroprotection in advanced breast cancer. Cancer Chemother Pharmacol 26 (suppl) S87-S90, 1990Google Scholar
  18. 18.
    Fields KK, Elfenbein GJ, Kloke O: Ifosfamide, carboplatin and etoposide (ICE) combination chemotherapy in refractory, metastatic breast cancer - Preliminary results. (abstract) Breast Cancer Res Treat 16: 159, 1990Google Scholar
  19. 19.
    Hoffmann W, Weidmann B, Migeod F, Konner J, Seeber S: Epirubicin and ifosfamide in patients with refractory breast cancer and other metastatic solid tumours. Cancer Chemother Pharmacol 26 (suppl) S69-S70, 1990Google Scholar
  20. 20.
    Schmid H, Kaufmann M, Grischke E-M, Bastert G: Ifosfamide combination chemotherapy in advanced breast cancer. Cancer Chemother Pharmacol 26 (suppl): S71-S73, 1990Google Scholar
  21. 21.
    Ghavamzadeh A: Treatment of metastatic breast cancer with the combination of ifosfamide, epirubicin and 5-fluorouracil. Cancer Chemother Pharmacol 26 (suppl): S66-S68, 1990Google Scholar
  22. 22.
    Nicholson S, Sainsbury JRC, Halcrow P, Chambers P, Farndon JR, Harris AL: Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer. Lancet 333: 182–185, 1989Google Scholar
  23. 23.
    Cantwell BMJ, Hennessy C, Millward M, Lennard TWJ: Epidermal growth factor receptors and doxorubicin plus ifosfamide/mesna in recurrent breast cancer. Lancet 337: 1417, 1991Google Scholar
  24. 24.
    Harris AL, Cantwell BMJ, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RGB: Comparison of short-term and continuous chemotherapy (mitoxantrone) for advanced breast cancer. Lancet 335: 186–190, 1990Google Scholar
  25. 25.
    Coates A, Gebski V, Bishop JF, Jeal PN, Woods RL, Snyder R, Tattersall MNH, Byrne M, Harvey V, Gill G, Simpson J, Drummond R, Browne J, van Gooten R, Forbes JF: Improving the quality of life during chemotherapy for advanced breast cancer: a comparison of intermittent and continuous treatment strategies. N Engl J Med 317: 1490–1495, 1987Google Scholar
  26. 26.
    Nash CH, Jones SE, Moon TE, Davis SL, Salmon AE: Prediction of outcome in metastatic breast cancer treated with adriamycin combination chemotherapy. Cancer 46: 2380–2388, 1980Google Scholar
  27. 27.
    Jones SE, Durie BGM, Salmon SE: Combination chemotherapy with adriamycin and cyclophosphamide for advanced breast cancer. Cancer 36: 90–97, 1975Google Scholar
  28. 28.
    Buzdar AU, Legha SS, Tashima CK, Yap H-Y, Hortobagyi GN, Hersh EM, Blumenschein GR, Bodey GP: Ifosfamide versus cyclophosphamide in combination drug therapy for metastatic breast cancer. Cancer Treat Rep 63: 115–120, 1979Google Scholar
  29. 29.
    Lind MJ, Cantwell B, Millward MJ, Gumbrell L, Proctor M, Simmonds D, Chapman F, Calvert AH: The use of rHGCSF to accelerate the delivery of ifosfamide and epirubicin in women with locally advanced or metastatic carcinoma of the breast. (abstract) Proc Am Assn Cancer Res 33: 242, 1992Google Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Michael Millward
    • 1
  • Michael Lind
    • 1
  • Lindsey Gumbrell
    • 1
  • Angela Robinson
    • 1
  • Thomas Lennard
    • 2
  • Brian Cantwell
    • 1
  1. 1.Newcastle General Hospital, Newcastle Upon TyneUniversity Department of Clinical OncologyUK
  2. 2.Royal Victoria Infirmary, Newcastle Upon TyneUniversity Department of SurgeryUK

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