Abstract
Aims.Anthracyclines-taxanes containing regimens are widely used for breast cancer treatment both in neoadjuvant–adjuvant setting and in metastatic disease. Recently high-dose chemotherapy (HDC) with autologous stem cell support has been introduced as adjuvant treatment for high-risk primary breast cancer and for selected subsets of women with metastatic disease. Therefore, salvage treatment for previously treated patients with progressive disease becomes even more problematic. A regimen of continuous infusion of fluorouracil (FU) and vinorelbine (VNR) has been evaluated in heavily pretreated metastatic breast cancer patients.
Patients and methods.Forty-eight women, median age 52 years, with previously treated breast cancer entered the study. All but one received more than one line of prior systemic chemotherapy for metastatic disease. Furthermore 14 women had undergone HDC with peripheral blood progenitor cells transplantation in adjuvant setting (6 pts), or metastatic disease (8 pts). Treatment consisted of four-day infusion of FU (1000 mg/m2/day) plus VNR (20 mg/m2/iv. day 1 and 5), recycled every 3 weeks for a total of six courses. Drugs administration was discontinued for G4 toxicity, tumor progression or patient's refusal.
Results.Twenty PR and four CR for an overall response rate of 50% (95%C.I. 36–64%) were recorded. The therapeutic efficacy of the tested regimen was documented both in patients unresponsive to previous anthracyclines-taxanes combinations and in those relapsing after HDC. The median duration of response was 9 months and median survival 16 months. One third of patients experienced Grade-3 stomatitis–mucositis, hematological toxicity was mild and no cardiac toxicity was observed. Twentyfive women (52%) suffered from infusion-related phlebitis (in half of patients a central venous device was necessary at some point of the treatment program).
Conclusions.The combination of FU infusion and VNR iv is an effective salvage treatment for heavily pretreated metastatic breast cancer patients, and may represent a valid alternative when other cytotoxic regimens are not feasible.
Similar content being viewed by others
References
Bonadonna G, Valagussa P: Primary chemotherapy in operable breast cancer. Semin Oncol 23: 464–474, 1996
Bonadonna G: Current and future trends in the multidisciplinary approach of high-risk breast cancer: the experience of the Milan Cancer Institute. Eur J Cancer 32A: 209–214, 1996
Henderson IC, Berry D, Demetri G, Cirrincione C, Goldstein L, Martino S, Ingle JN, Cooper MR, Canellos G, Borden E, Fleming G, Holland JF, Graziano S, Carpenter J, Muss H, Norton L: Improved disease-free and overall survival from the addition of sequential paclitaxel, but not from the escalation of doxorubicin dose level in the adjuvant chemotherapy of patients with node positive primary breast cancer. Proc Am Soc Clin Oncol 17: 101a, Abstr 390A, 1998
Peters WP, Ross M, Vredenburg JJ, Meisenberg B, Marks LB, Winer E, Kurtzeberg J, Bast RC jr, Jones R, Shpall E, Wu K, Rosner G, Gilbert C, Mathias B, Coniglio D, Petros W, Craig Henderson I, Norton L, Weiss R, Budman D, Hurd D: High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose therapy for high-risk primary breast cancer. J Clin Oncol 11: 1132–1143, 1993
Gianni AM, Siena S, Bregni M, Di Nicola M, Orefice S, Cusumano F, Salvadori B, Luini A, Greco M, Zucali R, Rilke F, Zambetti M, Valagussa P, Bonadonna G: Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five year results. J Clin Oncol 15: 2312–2321, 1997
Bezwoda WR, Seymour L, Dansey RD: High-dose chemotherapy with hematopoletic rescue as primary treatment for metastatic breast cancer: a randomized clinical trial. J Clin Oncol 13: 2483–2489, 1995
Rowinsky EK, Eisenhauer EA, Chauadrhy U, Arbuck S, Donehower CR: Paclitaxel (Taxol) Investigators' Workshop. Semin Oncol 20(Suppl. 3): 1–60, 1993
Aapro MS, Lavelle F, Bissery MC, Ravdin P, Fossella F, Kaye SB: The impact of docetaxel (Taxotere) on current treatment. Semin Oncol 22(Suppl. 4): 1–33, 1995
Abeloff MD, Hayes DF, Henderson IC: The current status of vinorelbine (Navelbine) in breast cancer. Semin Oncol 22 (Suppl. 5): 1–87, 1995
Degardin M, Bonneterre J, Hecquet B, Pion JM, Adenis H, Homer D, Demaille A: Vinorelbine (Navelbine) as salvage treatment of advanced breast cancer. Ann Oncol 5: 423–426, 1994
Hansen RM: 5-fluorouracil by protracted intravenous infusion: a review of recent clinical studies. Cancer Invest 9: 637–642, 1991
Ng JS, Cameron DA, Leonard RCF: Infusional 5-fluorouracil in breast cancer. Cancer Treat Rev 20: 357–364, 1994
Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Ruben RD: Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289–1294, 1977
Alexander J, Dainiak N, Berger HJ, Goldman L, Johnstone D, Reduto L, Dufty T, Schwartz P, Gottschalk A, Zaret B: Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide cardioangiography. N Engl J Med 300: 278–283, 1979
Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 47: 207–214, 1981
Kaplan EL, Meier P: Nonparametric estimation for incomplete observation. J Am Stat Assoc 135: 185–198, 1958
Peto R, Peto J: Asymptotically efficient rank invariant test procedures. J P Stat Soc(A) 34: 187–220, 1972
Pedrazzoli P, Perotti C, Da Prada GA, Battaglia M, Pavesi L, Preti P, Salvaneschi L, Robustelli della Cuna G: Collection of circulating progenitor cells after epirubicin, paclitaxel and filgrastim in patients with metastatic breast cancer. Br J Cancer 75: 1368–1379, 1997
Hortobagyi GN: Treatment of breast cancer. N Engl J Med 339: 974–984, 1998
Rowinsky EK, Donehower RC: Paclitaxel (Taxol). N Engl J Med 332: 1004–1014, 1995
Singal PK, Iliskovic N: Doxorubicin-induced cardiomiopathy. N Engl J Med 339: 900–905, 1998
Norton L: Salvage chemotherapy of breast cancer. Semin Oncol 21 (Suppl 7): 19–24, 1994
Dieras V, Extra LM, Bellisant E, Espie M, Morvan F, Pierga JY, Mignot L, Tresca P, Marty M: Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method. J Clin Oncol 14: 3097–3104, 1996
Vogel M, Hochster H, Blumreich M, Davis H, Graham M, Fabian C, Laufman L, Steinfeldt H, Hohneker J: A US multicenter phase II study of iv Navelbine (NVB) and 5 fluorouracil (5FU) as first line treatment of patients with advanced breast cancer (ABC). Proc Am Soc Clin Oncol 14: 91, Abstract 62, 1995
Zambetti M, Demicheli R, De Candis D, Antonelli G, Terenziani M, Laifranchi A, Garbagnati F, Biasi S, Bonadonna G: Five-day infusion fluorouracil plus vinorelbine iv in metastatic pretreated breast cancer. Breast Cancer Res Treat 44: 255–260, 1997
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zambelli, A., Robustelli della Cuna, F., Ponchio, L. et al. Four-day infusion of fluorouracil plus vinorelbine as salvage treatment of heavily pretreated metastatic breast cancer. Breast Cancer Res Treat 61, 241–247 (2000). https://doi.org/10.1023/A:1006462023110
Issue Date:
DOI: https://doi.org/10.1023/A:1006462023110