Abstract
In this phase II trial we have evaluatedthe activity and toxicity of a combination regimencontaining mitoxantrone, L-leucovorin, and fluorouracil in patients withadvanced breast cancer pretreated with anthracyclines. Forty-six patientswere included into the study; they received atotal of 227 cycles of chemotherapy. Median agewas 63 years (range 34–78), median performance statuswas 80 (range 60–100). Visceral metastases were presentin 37 patients, 6 patients had bone involvementonly, while 3 patients had soft tissue/lymph nodedisease. Median number of previous chemotherapy regimens foradvanced disease was 2 (range 1–3). Ten patientshad anthracycline primary resistance (progressive disease during treatment).Twenty-three patients received mitoxantrone 12 mg/sqm day 1;fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqmdays 1–3 administered every three weeks. Another groupof 23 patients were treated with the sameregimen using a prolonged 5FU/L-FA schedule (5 days).Two complete responses and 6 partial responses wererecorded with the 3-day schedule; 7 partial responsesin the 5-day schedule (overall response rate 32.6%,95% C.I. 19–46%). Two partial responses were observedin patients with anthracycline primary resistance. Median responseduration was 9 months (range 3–16). Hematologic toxicitywas mild: grade 3–4 leukopenia was recorded in5 patients, grade 3–4 thrombocytopenia in 3 patients.Grade III–IV stomatitis and diarrhea was recorded in4 and 5 patients respectively (all receiving the5-day 5-FU/L-FA schedule). Cardiac toxicity was observed intwo cases. This regimen proved active in advancedbreast cancer following anthracycline-containing chemotherapy, and the 3-dayschedule could be offered to such patients withacceptable toxicity.
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Henderson IC, Harris JR: Principles in the management of metastatic disease. In: Harris JR, Hellman S, Henderson IC, Kinne D (eds) Breast Disease (ed. 2). Lippincott, Philadelphia, PA, 1991, pp 627
Swain SM, Lippman 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
Doroshow JH, Leong L, Margolin K, Flanagan B, Goldberg D, Bertrand M, Akman S, Carr B, Odujinrin O, Newman E: Refractory metastatic breast cancer: Salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium. J Clin Oncol 7: 439–444, 1989
Hainsworth JD, Andrews MB, Johnson DH, Greco FA: Mitoxantrone, fluorouracil and high-dose leucovorin: An effective, well-tolerated regimen for metastatic breast cancer. J Clin Oncol 9: 1731–1736, 1991
Jones SE, Mennel RG, Brooks B, Westrik MA, Allison MA, 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
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: 2106–2108, 1993
Despax R, Gratet A: Combination chemotherapy of metastatic breast cancer with high-dose leucovorin, 5FU and mitoxantrone: Pilot study with escalating doses. Proc Am Soc Clin Oncol 10: 63, 1991 (abstr 127)
Swain S, Honig S, Johnson K, Egan E, Walton L, Pickle L, Tefft M, George M: 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 (abstr 89)
Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 47: 207–214, 1981
Porkka K, Blomqvist C, Rissanen P, Elomaa I, Pyrhönen S: Salvage therapies in women who failed to respond to first-line treatment with fluorouracil, epirubicin and cyclophosphamide for advanced breast cancer. J Clin Oncol 12: 1639–1647, 1994
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
Jolivet J, Belanger K, Yelle L, Guevin R, Potvin M, Wilson J, Rudinskas L, Latreille J, Dionne J, Gagne L, Aioub J: The importance of dose scheduling with mitoxantrone, 5-fluorouracil and leucovorin in metastatic breast cancer. Eur J Cancer 30A: 626–628, 1994
Zaniboni A, Meriggi F, Arcangeli G, Marpicati P, Montini E, Simoncini E, Marini G: L-folinic acid and fluorouracil in the treatment of advanced breast cancer: A phase II study. Ann Oncol 2: 41–43, 1993 (Suppl 2)
Seidman AD, Reichman BS, Crown JP, Yao TJ, Currie V, Hakes TB, Hudis CA, Gilewski TA, Baselga J, Forsythe P, Lepore J, Marks L, Fain K, Souhrada M, Onetto N, Arbuck S, Norton L: Paclitaxel as second and subsequent therapy for metastatic breast cancer: activity independent of prior anthracycline response. J Clin Oncol 13: 1152–1159, 1995
Wilson WH, Berg SL, Bryant G, Wittes RE, Bates S, Foio A, Steinberg SM, Goldspiel BR, Herdt J, O'Shaughnessy J, Balis FM, Chabner BA: Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: A Phase I–II trial of 96-hour infusion. J Clin Oncol 12: 1621–1629, 1994
Hainsworth JD, Jones SE, Mennel RG, Blum JL, Greco FA: Paclitaxel with mitoxantrone, fluorouracil and high dose leucovorin in the treatment of metastatic breast cancer: A phase II trial. J Clin Oncol 14: 1611–1616, 1996
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Bascioni, R., Giorgi, F., Silva, R.R. et al. Mitoxantrone, fluorouracil, and L-folinic acid in anthracycline-pretreated metastatic breast cancer patients. Breast Cancer Res Treat 45, 205–210 (1997). https://doi.org/10.1023/A:1005856028736
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DOI: https://doi.org/10.1023/A:1005856028736