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Salvage chemotherapy in metastatic breast cancer: An experience with the combination of mitoxantrone, 5-fluorouracil, and L-leucovorin

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Summary

From January 1992 to July 1993, 28 patients with metastatic breast cancer were entered in a phase II trial to assess the activity and toxicity of the combination of mitoxantrone, 5-fluoruracil, and leucovorin. Patients were eligible if they had progressive disease after either adjuvant (2 patients) or previous chemotherapy for metastatic disease (26 patients). Twenty-five patients (89.2%) had received previous anthracycline-based therapy. Predominant site of metastatic disease was visceral in 22 patients, bone in 2 patients, soft tissue in 4 patients, and the majority of patients (89.2%) had two or more sites of disease. The regimen was administered according to the following schedule: Mitoxantrone 9–12 mg/m2 i.v. on day 1; L-Leucovorin 150 mg i.v. over 1 hour before 5-Fluorouracil 350 mg/m2 i.v. push days, 1, 2 and 3. Courses were repeated every 21 days. Twenty-six patients were evaluable for response. We observed 2 complete responses, 5 partial responses with a median duration of 38 weeks (range 23–68). The objective response rate was 27% (95% C.I., 10% to 44%). Myelo-suppression was the most frequent toxicity, but it was mild in the majority of patients. Nine episodes of fever and neutropenia occurred in six patients but none of these episodes was fatal. No clinical evidence of cardiotoxicity was observed.

At a median follow-up of 78 weeks, the median time to progression was 20.5 weeks and the median overall survival was 48 weeks.

We conclude that this regimen is well tolerated and in our experience the objective response rate is similar to other salvage chemotherapy regimens.

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References

  1. Canellos GP, DeVita VT, Gold GL, Chabner BA, Schein PS, Young RC: Combination chemotherapy for advanced breast cancer: response and effect on survival. Ann Intern Med 84: 389–392, 1976

    PubMed  Google Scholar 

  2. Falkson G, Gelman RS, Tormey DC, Cummings FJ, Carbone PP, Falkson HC: The Eastern Cooperative Oncology Group experience with cyclophosphamide, adriamycin and 5-fluoruracil (CAF) in patients with metastatic breast cancer. Cancer 56: 219–224, 1985

    PubMed  Google Scholar 

  3. Eddy DM: High-dose chemotherapy with autologous bone marrow transplantation for the treatment of metastatic breast cancer. J Clin Oncol 10: 657–670, 1992

    PubMed  Google Scholar 

  4. Landys K, Borgstrom S, Anderson T, Noppa H: Mitoxantrone as a first-line treatment of advanced breast cancer. Invest New Drugs 3: 133–137, 1985

    PubMed  Google Scholar 

  5. Smith IE, Stuart-Harris R, Pavlidis N, Bozek T: Mitoxantrone as single agent and in combination chemotherapy in the treatment of advanced breast cancer. Cancer Treat Rev 10: 37–40, 1983

    PubMed  Google Scholar 

  6. Mouridsen HT, Cornbleet M, Stuart-Harris R, Smith I, Coleman R, Rubens R, McDonald M, Rainer H, van Oosterom A, Smyth J: Mitoxantrone as first-line chemotherapy in advanced breast cancer: results of a Collaborative European Study. Invest New Drugs 3: 139–148, 1985

    PubMed  Google Scholar 

  7. Smyth IE, Cornbleet MA, Stuart-Harris RC, Smith IE, Coleman RE, Rubens RD, McDonald M, Mouridsen HT, Rainer H, van Oosterom AT: Mitoxantrone as first-line chemotherapy for advanced breast cancer: results of a European Collaborative Study. Sem Oncol 11: 15–18, 1984

    Google Scholar 

  8. Shenkenberg TD, Von Hoff DD: Mitoxantrone: a new anticancer drug with significant clinical activity. Ann Intern Med 105: 67–81, 1986

    PubMed  Google Scholar 

  9. Neidhart JA, Gachnour D, Roach R, Hoth D, Young D: A comparison of mitoxantrone and doxorubicin in breast cancer. J Clin Oncol 4: 672–677, 1986

    PubMed  Google Scholar 

  10. Henderson IC, Allegra JC, Woodcock T, Wolff S, Bryan S, Cartwright K, Dukart G, Henry D: Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol 7: 560–571, 1989

    PubMed  Google Scholar 

  11. Doroshow JH, Multhauf P, Leong L, Margolin K, Litchfield T, Akman S, Carr B, Bertrand M, Golberg D, Blayney D, Odujinrin O, DeLap R, Shuster J, Newman E: Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. J Clin Oncol 8: 491–501, 1990

    PubMed  Google Scholar 

  12. Petrelli N, Douglass HO, Herrera L, Russell D, Stablein DM, Bruckner HW, Mayer RJ, Schinella R, Green MD, Muggia FM, Megibow A, Greenwald ES, Bukowski RM, Harris J, Levin B, Gaynor E, Loutfi A, Kalser MH, Barkin JS, Benedetto P, Woolley PV, Nauta R, Weaver DW, Leichman LP: The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. J Clin Oncol 7: 1419–1426, 1989

    PubMed  Google Scholar 

  13. Swain SM, Lippmann ME, Egan EF, Drake JC, Steinberg SM, Allegra CJ: Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. J Clin Oncol 7: 890–899, 1989

    PubMed  Google Scholar 

  14. Doroshow JH, Leong L, Margolin K, Flanagan B, Goldberg D, Bertrand M, Akman S, Carr B, Odujinrin O, Newman E, Litchfield T: Refractory metastatic breast cancer: salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium. J Clin Oncol 7: 439–444, 1989

    PubMed  Google Scholar 

  15. Loprinzi CL, Ingle JN, Schaid DJ, Bukner JC, Edmond JH, Allegra CJ: 5-fluorouracil plus leucovorin in women with metastatic breast cancer. Am J Clin Oncol 14: 30–32, 1991

    PubMed  Google Scholar 

  16. Fine S, Erlichman C, Kaizer L, Warr D, Elhakim T: Phase II trial of 5-FU + folinic acid (FA) as first line treatment for metastatic breast cancer. Proc Am Soc Clin Oncol 7: 41, 1988

    Google Scholar 

  17. Hainsworth DJ, Andrews MB, Johnson DH, Greco A: Mitoxantrone, fluorouracil, and high-dose leucovorin: an effective, well-tolerated regimen for metastatic breast cancer. J Clin Oncol 9: 1731–1733, 1991

    PubMed  Google Scholar 

  18. Jones SE, Mennel RG, Brooks B, Westrick MA, Allison A, Paulson RS, Tilmann K, Rea B: Phase II study of mitoxantrone, leucovorin, and infusional fluorouracil for treatment of metastatic breast cancer. J Clin Oncol 9: 1736–1739, 1991

    PubMed  Google Scholar 

  19. Newman EM, Straw JA, Doroshow JH: Pharmacokinetics of diastereoisomers of (6R,S)-folinic acid (Leucovorin) in humans during constant high-dose intravenous infusion. Cancer Res 49: 5755–5760, 1989

    PubMed  Google Scholar 

  20. Machover D, Grison X, Goldschmidt E, Zittoun J, Lotz JP, Metzger G, Richaud J, Hannoun L, Marquet J, Guillot T, Salmon R, Sezeur A, Mauban S, Parc R, Izrael V: Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: A Phase I–II study. J Natl Cancer Inst 84: 321–327, 1992

    PubMed  Google Scholar 

  21. Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 47: 207–214, 1981

    PubMed  Google Scholar 

  22. Roila F, Basurto C, Minotti V, Ballatori E, Tonato M: A phase II antiemetic combination (COMD) for cisplatin-induced nausea and vomiting. Cancer Chemother Pharmacol 18: 88–89, 1986

    PubMed  Google Scholar 

  23. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Statist Assoc 53: 457–481, 1958

    Google Scholar 

  24. Wils JA: Mitoxantrone, leucovorin and high-dose infusional 5-fluorouracil: an effective and well-tolerated regimen for the treatment of advanced breast cancer. Eur J Cancer 29A (15): 2106–2108, 1993

    PubMed  Google Scholar 

  25. Repetto L, Miglietta L, Gardin G, Lanfranco C, Naso C, Merlini L, Giudici S, Venturino A, Campora E, Testore F, Rosso R: Phase II study of weekly mitoxantrone, 5-fluorouracil, and leucovorin in metastatic breast cancer. Breast Cancer Res Treat 30: 133–137, 1994

    PubMed  Google Scholar 

  26. Swain S, Honig S, Johnson K, Egan E, Walton L, Pickle L, Tefft M, George M, Vincenti T: A mitoxantrone, 5-fluorouracil and high dose leucovorin regimen as treatment for patients with metastatic breast cancer. Proc Am Soc Clin Oncol 10: 54, 1991

    Google Scholar 

  27. Bonadonna G, Valagussa P: Chemotherapy of breast cancer. Current views and results. Int J Radiat Oncol Biol Phys 9: 279–297, 1983

    PubMed  Google Scholar 

  28. Hortobagyi GN: Salvage chemotherapy for metastatic breast cancer. Sem Hematol 24: 56–61, 1987

    Google Scholar 

  29. Belanger K, Dionne J, Yelle L, Blais M, Ayoub J, Jolivet J: First-line combination chemotherapy of metastatic breast cancer with mitoxantrone, 5-fluorouracil and high dose leucovorin. Proc Am Soc Clin Oncol 9: 31, 1990

    Google Scholar 

  30. Carmo-Pereira J, Costa FO, Henriques E: Mitoxantrone, folinic acid, 5-fluorouracil and prednisone, as first-line chemotherapy in advanced breast cancer. A phase II study. Proc Am Soc Clin Oncol 10: 50, 1991

    Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Division, Policlinico Hospital, via Brunamonti, 06100, Perugia, Italy

    Mariantonietta Colozza, Stefania Gori, Anna Maria Mosconi, Paola Anastasi, Carlo Basurto, Vienna Ludovini & Maurizio Tonato

  2. Medical Statistics Unit, University of Perugia, Italy

    Verena De Angelis

  3. Department of Pathology, University of Perugia, Italy

    Michele Giansanti

Authors
  1. Mariantonietta Colozza
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  2. Stefania Gori
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  3. Anna Maria Mosconi
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  4. Paola Anastasi
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  5. Carlo Basurto
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  6. Vienna Ludovini
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  7. Verena De Angelis
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  8. Michele Giansanti
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  9. Maurizio Tonato
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Colozza, M., Gori, S., Mosconi, A.M. et al. Salvage chemotherapy in metastatic breast cancer: An experience with the combination of mitoxantrone, 5-fluorouracil, and L-leucovorin. Breast Cancer Res Tr 38, 277–282 (1996). https://doi.org/10.1007/BF01806146

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