Fluorouracil and Mitomycin: An Option for Metastatic Breast Cancer

Zusammenfassung

Fragestellung: Die Therapie von Patientinnen mit einem metastasierten, anthrazyklinresistenten Mammakarzinom bleibt weiterhin eine Herausforderung. Mitomycin C besitzt eine bemerkenswerte therapeutische Aktivität beim metastasierten MaCa und zeigt additive Effekte mit 5-Fluorouracil. Das Ziel der retrospektiven Analyse war die Ermittelung der Effektivität und Toxizität der Kombination beider Substanzen in der Therapie des metastasierten Mammakarzinoms. Material und Methodik: 25 Patientinnen erhielten insgesamt 121 Zyklen Mitomycin C 7 mg/m², d1, und 5-Fluorouracil 750 mg/m²/d, d1-5, q21d (FUMI-Schema). Ergebnisse: Die mediane Zeit bis zur Progression lag bei 6,9 Monaten und das mediane Überleben war 10,52 Monate. Neun Patientinnen (39,1 %) zeigten ein objektives Ansprechen. Zwei Patientinnen (8,7 %) erreichten eine komplette Remission. Die meisten therapiebedingten unerwünschten Ereignisse hatten eine milde bis mäßige Intensität. Schlussfolgerung: Zusammenfassend zeigte die Therapie mit Mitomycin C und 5-Fluorouracil ein günstiges Nebenwirkungsprofil. Die Kombination wird gut vertragen und zeigt ein bemerkenswertes Ansprechen in der palliativen Therapiesituation.

Abstract

Purpose: The treatment of metastatic breast cancer in patients previously treated with anthracycline represents a significant challenge. Mitomycin C has notable therapeutic activity in metastatic breast cancer, and 5-fluorouracil has additive effects. The aim of this retrospective analysis was to evaluate the efficacy and toxicity of a combination of the two agents in patients with metastatic breast cancer. Materials and Methods: Twenty-five patients received a total of 121 cycles of mitomycin C 7 mg/m² on day 1 and 5-fluorouracil 750 mg/m²/d on days 1 - 5, q21d. Results: The median time to progression was 6.9 months and the median survival was 10.52 months. Nine patients (39.1 %) achieved an objective response, including two (8.7 %) with complete responses. Most treatment-related adverse events were mild to moderate in intensity. Conclusion: In conclusion the treatment with mitomycin C and 5-fluorouracil showed a favourable safety profile. The combination is well tolerated and active in this setting.

Schlüsselwörter

Mitomycin C - 5-Fluorouracil - metastasiertes Mammakarzinom - palliative Chemotherapie

Key words

Mitomycin C - 5-fluorouracil - palliative chemotherapy - metastatic breast cancer

References

• 1 Stockler M, Wilcken N R, Ghersi D, Simes R J. Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer.  Cancer Treat Rev. 2000;  26 151-168
• 2 Nabholtz J M, Tonkin K, Smylie M, Au H J, Lindsay M A, Mackey J. Chemotherapy of breast cancer: are taxanes going to change the natural history of breast cancer?.  Expert Opin Pharmacother. 2000;  1 187-206
• 3 Garewal H S. Mitomycin C in the chemotherapy of advanced breast cancer.  Semin Oncol. 1988;  15 74-79
• 4 Francini G, Petrioli R, Messinese S. et al . Folinic acid, 5-fluorouracil and mitomycin C in metastatic breast cancer patients previously treated with at least two chemotherapy regimens.  Cancer Chemother Pharmacol. 2002;  50 271-276
• 5 Joensuu H, Holli K, Heikkinen M. et al . Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.  J Clin Oncol. 1998;  16 3720-3730
• 6 French Epirubicin Study Group . A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin.  J Clin Oncol. 1988;  6 679-688
• 7 Seitz J F, Diaw A, Giovannini M, Perrier H, Gouvernet J. 5-Fluorouracil, high dose folinic acid and mitomycin C in the treatment of advanced digestive cancers.  Bull Cancer. 1994;  81 134-137
• 8 Loibl S, von Minckwitz G, Schwedler K. et al . Mitomycin C, 5-fluorouracil and folinic acid (Mi-Fu-Fo) as salvage chemotherapy in breast cancer patients with liver metastases and impaired hepatic function: a phase II study.  Anticancer Drugs. 2004;  15 719-724
• 9 Stamatovic L, Jelic S, Susnjar S, Vasovic S, Tomasevic Z, Neskovic-Kontantinovic Z. Final results of phase II study of docetaxel-mitomycin-vinblastine combination chemotherapy in patients with anthracycline-resistant metastatic breast cancer.  Ann Oncol. 2002;  13 67
• 10 Baur M, Kienzer H, DeSantis M. et al . Effective salvage therapy with carboplatin/mitomycin C in metastatic breast cancer.  Onkologie. 2002;  25 249-254
• 11 Falcone A, Cianci C, Pfanner E. et al . Continuous-infusion 5-fluorouracil in metastatic colorectal cancer patients pretreated with bolus 5-fluorouracil: clinical evidence of incomplete cross-resistance [letter].  Ann Oncol. 1994;  5 291
• 12 Hansen R, Quebbeman E, Beatty P. et al . Continuous 5-fluorouracil infusion in refractory carcinoma of the breast.  Breast Cancer Res Treat. 1987;  10 145-149
• 13 Jabboury K, Holmes F A, Hortobagyi G. 5-Fluorouracil rechallenge by protracted infusion in refractory breast cancer.  Cancer. 1989;  64 793-797
• 14 Crooke S T, Bradner W T. Mitomycin C: a review.  Cancer Treat Rev. 1976;  3 121-139
• 15 Dieras V, Marty M, Tubiana N. et al . Phase II randomized study of paclitaxel versus mitomycin in advanced breast cancer.  Semin Oncol. 1995;  22 33-39
• 16 Bernardo G, Plastina M, Cucchi M, Strada M RB. Mitomycin C (MMC) and 5-fluorouracil (FU) in the treatment of advanced pretreated breast carcinoma [abstract].  Ann Oncol. 1990;  1 (26) 37
• 17 Geberth M. et al . Second-line chemotherapy of patients with metastatic breast cancer after failure of anthracyclines with mitomycin, folinate and 5-fluorouracil [abstract].  J Cancer Res Clin Oncol. 2000;  126: R93/S0222 32
• 18 Heinemann V. Role of gemcitabine in the treatment of advanced and metastatic breast cancer.  Oncology. 2003;  64 191-206
• 19 Winer E P, Morrow M, Osborne C K, Harris J R. Malignant tumors of the breast. DeVita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. Philadelphia; Lippincott-Raven 2001: 1651-1717
• 20 Henderson I C. Principles in the management of metastatic disease: chemotherapy for metastatic disease. Harris JR Breast Diseases. Philadelphia; Lippincott 1991: 604-665
• 21 Abrams J S, Vena D A, Baltz J. et al . Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.  J Clin Oncol. 1995;  13 2056-2065
• 22 Valero V, Holmes F A, Walters R S. et al . Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.  J Clin Oncol. 1995;  13 2886-2894
• 23 Blum J L, Dieras V, Lo Russo P M. et al . Multicenter, phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients.  Cancer. 2001;  92 1759-1768
• 24 Fumoleau P, Largillier R, Clippe C. et al . Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer.  Eur J Cancer. 2004;  40 536-542