Skip to main content

Advertisement

SpringerLink
Log in

Etoposide, mitomycin, and methotrexate combination in heavily treated breast cancer: a retrospective study

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Background

Since 2004, metastatic breast cancer patients pretreated with anthracyclines, taxanes, and capecitabine have been treated in our institution with a combination of mitomycin C, methotrexate, and VP-16 (VMM). We report in this study a retrospective analysis of the activity and safety of the VMM combination.

Methods

Patients were treated with a combination of VP-16 (100 mg/m2 on day 1), mitomycin C (MMC, 10 mg/m2 on day 1), and methotrexate (MTX, 12.5 mg/m2 twice a day on day 2 and 3) in a 21-day cycle.

Results

Seventy-five patients were treated. Median age was 48 years. A total of 256 cycles were administered. Median relative dose intensities were 0.87, 0.87, and 0.95 for VP-16, MMC, and MTX, respectively. Objective response rate was 31%, with a clinical benefit rate of 47%. Median response duration was 5.8 months. Median disease stabilization duration was 9.1 months. Median progression-free survival (PFS) was 4.2 months with a 14% 1-year PFS rate. Median overall survival (OS) was 6.2 months, with a 25% 1-year OS rate. Myelosuppression was the most common toxicity. The most commonly reported extra-hematological adverse event (AE) was fatigue. Emesis and alopecia were rarely reported.

Conclusions

This combination appears to be effective and well tolerated in this heavily pretreated metastatic breast cancer population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Overmoyer B. Options for the treatment of patients with taxane-refractory metastatic breast cancer. Clin Breast Cancer. 2008;8(Suppl 2):S61–70.

    Article  PubMed  CAS  Google Scholar 

  2. Perez EA. Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer. Breast Cancer Res Treat. 2009;114(2):195–201.

    Article  PubMed  CAS  Google Scholar 

  3. Barnett CM. Survival data of patients with anthracycline- or taxane-pretreated or resistant metastatic breast cancer. Pharmacotherapy. 2009;29(12):1482–90.

    Article  PubMed  CAS  Google Scholar 

  4. Rha SY, Moon YH, Jeung HC, Kim YT, Sohn JH, Yang WI, et al. Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer. Breast Cancer Res Treat. 2005;90(3):215–21.

    Article  PubMed  CAS  Google Scholar 

  5. O’Shaughnessy JA, Clark RS, Blum JL, Mennel RG, Snyder D, Ye Z, et al. Phase II study of pemetrexed in patients pretreated with an anthracycline, a taxane, and capecitabine for advanced breast cancer. Clin Breast Cancer. 2005;6(2):143–9.

    Article  PubMed  Google Scholar 

  6. Brodowicz T, Kostler WJ, Moslinger R, Tomek S, Vaclavik I, Herscovici V, et al. Single-agent gemcitabine as second- and third-line treatment in metastatic breast cancer. Breast. 2000;9(6):338–42.

    Article  PubMed  CAS  Google Scholar 

  7. Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25(23):3407–14.

    Article  PubMed  CAS  Google Scholar 

  8. Onyenadum A, Gogas H, Markopoulos C, Bafaloukos D, Aravantinos G, Mantzourani M, et al. Mitoxantrone plus vinorelbine in pretreated patients with metastatic breast cancer. J Chemother. 2007;19(5):582–9.

    PubMed  CAS  Google Scholar 

  9. Jara-Sanchez C, Martin M, Garcia-Saenz JA, Barnada A, Fernandez-Aramburo A, Lopez-Vega JM, et al. Vinorelbine as a 96-hour continuous infusion in heavily pretreated patients with metastatic breast cancer: a cooperative study by the GEICAM group. Clin Breast Cancer. 2003;3(6):399–404.

    Article  PubMed  CAS  Google Scholar 

  10. van Oosterom AT, Powles TJ, Hamersma E, Smith IE, Engelsman E. A phase II study of mitomycin C in refractory advanced breast cancer. A multi-centre pilot study. Eur J Cancer. 1980;Suppl 1:275–6.

    PubMed  Google Scholar 

  11. Hortobagyi GN. Mitomycin: its evolving role in the treatment of breast cancer. Oncology. 1993;50(Suppl 1):1–8.

    Article  PubMed  Google Scholar 

  12. Bonadonna G, Moliterni A, Zambetti M, Daidone MG, Pilotti S, Gianni L, et al. 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ. 2005;330(7485):217.

    Article  PubMed  Google Scholar 

  13. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.

    Article  Google Scholar 

  14. Schell FC, Yap HY, Hortobagyi GN, Issell B, Esparza L. Phase II study of VP16–213 (etoposide) in refractory metastatic breast carcinoma. Cancer Chemother Pharmacol. 1982;7(2–3):223–5.

    PubMed  CAS  Google Scholar 

  15. Pouillart P, Palangie T, Jouve M, Garcia-Giralt E, Magdelenat H. Effectiveness of VM 26, mitomycine C and methotrexate in advanced breast cancer refractory to a four drug combination (author’s transl). Bull Cancer. 1979;66(5):485–90.

    PubMed  CAS  Google Scholar 

  16. Tanabe M, Ito Y, Tokudome N, Sugihara T, Miura H, Takahashi S, et al. Possible use of combination chemotherapy with mitomycin C and methotrexate for metastatic breast cancer pretreated with anthracycline and taxanes. Breast Cancer. 2009;16(4):301–6.

    Article  PubMed  Google Scholar 

  17. Powles TJ, Jones AL, Judson IR, Hardy JR, Ashley SE. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J Cancer. 1991;64(2):406–10.

    Article  PubMed  CAS  Google Scholar 

  18. Jodrell DI, Smith IE, Mansi JL, Pearson MC, Walsh G, Ashley S, et al. A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/methotrexate/5 FU (CMF) in the treatment of advanced breast cancer. Br J Cancer. 1991;63(5):794–8.

    Article  PubMed  CAS  Google Scholar 

  19. Saso R, Kulkarni S, Mitchell P, Treleaven J, Swansbury GJ, Mehta J, et al. Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone-based therapy for breast carcinoma. Br J Cancer. 2000;83(1):91–4.

    Article  PubMed  CAS  Google Scholar 

  20. Schell FC, Yap HY, Blumenschein G, Valdivieso M, Bodey G. Potential cardiotoxicity with mitoxantrone. Cancer Treat Rep. 1982;66(8):1641–3.

    PubMed  CAS  Google Scholar 

  21. Zubrod C, Schneiderman M, Frei EJ. Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard an triethylene thiophosphoramide. J Chron Dis. 1960;11:7–33.

    Article  Google Scholar 

  22. World Health Organization. WHO handbook for reporting the results of cancer treatment. Geneva;1979.

  23. Kaplan E, Meier P. Nonparametric estimation for incomplete observations. J Am Stat Assoc. 1958;53:457–81.

    Article  Google Scholar 

  24. Hryniuk WM, Goodyear M. The calculation of received dose intensity. J Clin Oncol. 1990;8(12):1935–7.

    PubMed  CAS  Google Scholar 

  25. Massacesi C, La Cesa A, Marcucci F, Pilone A, Rocchi MB, Zepponi L, et al. Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer. Oncology. 2006;70(4):294–300.

    Article  PubMed  CAS  Google Scholar 

  26. Smith IE, Powles TJ. MMM (mitomycin/mitoxantrone/methotrexate): an effective new regimen in the treatment of metastatic breast cancer. Oncology. 1993;50(Suppl 1):9–15.

    Article  PubMed  Google Scholar 

  27. Vahdat LT, Pruitt B, Fabian CJ, Rivera RR, Smith DA, Tan-Chiu E, et al. Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2009;27(18):2954–61.

    Article  PubMed  CAS  Google Scholar 

  28. Ito Y, Osaki Y, Tokudome N, Sugihara T, Takahashi S, Iwase T, et al. Efficacy of S-1 in heavily pretreated patients with metastatic breast cancer: cross-resistance to capecitabine. Breast Cancer. 2009;16(2):126–31.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None to declare.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, CRLC Val d’Aurelle, 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France

    Kais Aldabbagh, Stéphane Pouderoux, Michel Fabbro, Gilles Romieu & William Jacot

  2. Department of Biostatistics, CRLC Val d’Aurelle, Montpellier, France

    Lise Roca

  3. Oncopharmacology Department, CRLC Val d’Aurelle, Montpellier, France

    Sylvain Poujol

Authors
  1. Kais Aldabbagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stéphane Pouderoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lise Roca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sylvain Poujol
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michel Fabbro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gilles Romieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. William Jacot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William Jacot.

About this article

Cite this article

Aldabbagh, K., Pouderoux, S., Roca, L. et al. Etoposide, mitomycin, and methotrexate combination in heavily treated breast cancer: a retrospective study. Breast Cancer 19, 16–22 (2012). https://doi.org/10.1007/s12282-010-0240-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-010-0240-7

Keywords

Search

Navigation