Summary
One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m2) or mitoxantrone (12 mg/m2) associated with 5-fluorouracil (600 mg/m2) and cyclophosphamide (600 mg/m2) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m2 day 1, Vbl 5 mg/m2 days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer. M-Vbl treatment is useful as second-line treatment in patients with prior adriamycin exposure.
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References
Henderson IC: Principles in the management of metastatic disease. Chemotherapy for metastatic disease.In: Harris JR, Hellman S, Henderson IC, Kinne DW (eds) Breast Diseases. J.B. Lippincott Company, Philadelphia, 1991, pp 604–665
Greenspan EM, Fieber M, Lesnick G, Edelman S: Response of advanced breast carcinoma to the combination of the antimetabolite, methotrexate, and the alkylating agent, thiotepa. J Mt Sinai Hospital 30: 246–267, 1963
Cooper RG: Combination chemotherapy in hormone resistant breast cancer. Proc Am Assoc Cancer Res 10: 15, 1969
Yap HY, Blumenschein GR, Schell FC, Buzdar AU, Valdivieso M, Bodey GP: Dihydroxyanthracenedione: A promising new drug in the treatment of metastatic breast cancer. Ann Intern Med 95: 694–697, 1981
Bull J, Tormey D, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R: A randomized comparative trial of Adriamycin versus methotrexate in combination drug therapy. Cancer 41: 1649–1657, 1978
Tormey DC, Weinberg VE, Leone LA, Glidewell OJ, Perloff M, Kennedy BJ, Cortes E, Silver RT, Weiss RB, Aisner J, Holland JF: A comparison of intermittent vs continuous and of Adriamycin vs methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study. Am J Clin Oncol 7: 231–239, 1984
Holmes FA, Yap H-Y, Esparza L, Buzdar AU, Hortobagyi GN, Blumenschein GR: Mitoxantrone, cyclophosphamide, and 5-fluorouracil in the treatment of hormone unresponsive metastatic breast cancer. Semin Oncol 11: 28–31, 1984 (suppl 1)
World Health Organization WHO Handbook for reporting results of cancer treatment. Geneva, WHO offset publication, n° 48, 1979
Fisher RA: Statistical Methods for Research Workers. Edinburgh University, Edinburgh, 1934
Pagano M, Halvorsen KT: An algorithm for finding the exact significance levels of rxc contingency tables. J Am Stat Assoc 76: 931–934, 1981
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958
Peto R, Peto J: Asymptotically efficient rank invariant test procedures. J R Stat Soc (A) 135: 185–206, 1972
Breslow N: Comparison of survival curves. In: Buyse ME, Staqut MJ, Sylvester RJ (eds) Cancer Clinical Trials, Methods and Practice. Oxford University Press, Oxford, 1984, pp 381–406
Neidhart JA, Gochnour D, Roach R, Young D: A comparison of mitoxantrone and doxorrubicin in breast cancer. J Clin Oncol 4: 672–677, 1986
Henderson IC, Wolff SN, Allegra JCet al.: A randomized trial comparing mitoxantrone and doxorubicin in patients with metastatic breast cancer. In: Coltman CA Jr (ed) The Current Status of Novantrone. John Wiley & Sons, New York, 1985, pp 45–53
Cowan JD, Neidhart J, McClure S, Coltman CA Jr, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CB, Osborne CK: Randomized trial of doxorubicin, bisantrene and mitoxantrone in advanced breast cancer: a Southwest Oncology Group Study. J Natl Cancer Inst 83: 1077–1084, 1991
Bennett JM, Byrne P, Desai A, White C, DeConti R, Vogel C, Krementz E, Muggia F, Doroshow J, Plotkin Det al.: A randomized multicenter trial of cyclophosphamide, Novantrone and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin and 5-fluorouracil (CAF) in patients with metastatic breast cancer. Invest New Drugs 3: 179–185, 1985
Bennett JM, Muss HB, Doroshow JH, Wolff S, Krementz E, Cartwright K, Dukart G, Reisman A, Schoch I: A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma. J Clin Oncol 6: 1611–1620, 1988
Stewart DJ, Maroun JA, Hirte W, Perrault D, Stolbach L, Cripps C, Lefebvre B: A randomized comparison of cyclophosphamide-mitoxantrone-5-fluorouracil vs cyclophosphamide-doxorubicin-5-fluorouracil in advanced breast cancer: preliminary observations. Semin Oncol 11: 23S-27S, 1984
Slater J, Green JA, Kelly V: Randomised trial of doxorubicin (A) against mitoxantrone (N) in combination in advanced breast cancer (abstract P-0885). London, Proc ECCO5, 1989
Heidemann E, Steinke B, Hartlapp J, Schumacher K, Possinger K, Kunz S, Neeser E, von Ingersleben G, Hossfeld D, Waldmann R: Randomized clinical trial comparing mitoxantrone with epirrubicin and with doxorubicin, each combined with cyclophosphamide in the first line treatment of patients with metastatic breast cancer. Onkologie 13: 24–27, 1990
Bailey N, Blackledge G, Chetiyawardana A, Larsson S, Latief T, Maciel C, Powell J: A controlled randomised study of cyclophosphamide and methotrexate together with either doxorubicin, epirubicin or mitoxantrone in advanced breast cancer (abstract P-0973). London, Proc ECCO5, 1989
Haller D, Andersen J, Muggia F, Tormey DC, Falkson G: Chemohormone therapy with Adriamycin (A) or mitoxantrone (M) combinations in advanced breast cancer: An Eastern Cooperative Oncology Group (ECOG) trial. Proc Am Soc Clin Oncol 7: 19, 1988
Periti P, Pannuti F, Robustelli Della Cuna G, Mazzei T, Mini E, Martoni A, Preti P, Ercolino L, Pavesi L, Ribecco A: Combination chemotherapy with cyclophosphamide, fluorouracil, and either epirubicin or mitoxantrone: a comparative randomized multicenter study in metastatic breast carcinoma. Cancer Invest 9: 249–255, 1991
Follezou JY, Palangie T, Feuilhade F: Essai randomise comparent la mitoxantrone a l'adriamycine dans les cancers du sein evolues. Presse Med 16: 765–768, 1987
Buyukunal E, Derman U, Serdengecti S, Berkada B: A clinical trial of mitoxantrone (novantrone) versus doxorubicin (adriamycin) in combination chemotherapy for metastatic breast cancer. Chemiotherapia 6: 377–379, 1987
Leonard RC, Cornbleet MA, Kaye SB, Soukop M, White G, Hutcheon AW, Robinson S, Kerr ME, Smyth JF: Mitoxantrone vs doxorubicin in combination chemotherapy for advanced carcinoma of the breast. J Clin Oncol 5: 1056–1063, 1987
Faulds D, Balfour JA, Chrisp P, Langtry MD: Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 41: 400–449, 1991
Denefrio JM, East DR, Troner MB, Vogel CL: Phase II study of mitomycin C and vinblastine in women with advanced breast cancer refractory to standard cytotoxic therapy. Cancer Treat Rep 62: 2113–2115, 1978
Konits P, Aisner J, VanEcho D, Lichtenfeld K, Wiernik P: Mitomycin C and vinblastine chemotherapy for advanced breast cancer. Cancer 48: 1295–1298, 1981
Garewal HS, Brooks RJ, Jones SE, Miller TP: Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine. J Clin Oncol 1: 772–775, 1983
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Alonso, M.C., Tabernero, J.M., Ojeda, B. et al. A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer. Breast Cancer Res Tr 34, 15–24 (1995). https://doi.org/10.1007/BF00666487
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DOI: https://doi.org/10.1007/BF00666487