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Toremifene and tamoxifen in advanced breast cancer - a double-blind cross-over trial

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Summary

Toremifene (TOR) is a triphenylethylene derivative related to tamoxifen (TAM). TOR has antitumor activity, not dependent on estrogen receptors, and responses with TOR have been observed in patients with progressive disease during TAM-treatment. To elucidate possible cross-resistance between these two antiestrogens, we compared their anti-tumor activity in a randomized, double-blind, cross-over study.

66 postmenopausal women with advanced estrogen receptor positive or unknown breast cancer and a median age of 63 years (range 38-82) were included. Patients were randomized to TAM 40mg/day or TOR 240mg/day. Treatment continued until progressive disease, when cross-over to the alternative treatment was done. The response rate with first line TOR was 29% (95% confidence limits 10–41%) and with TAM 42% (95% confidence limits 25–61%). Response rates and response durations, survival and toxicity were not significantly different between the two treatments. 44 patients progressing on first line TAM or TOR were evaluable for second line TOR or TAM treatment. As no responses were observed, the possibility of overlooking a response rate of 20% or more is less than 1%.

In conclusion, this study strongly indicates that TOR and TAM are clinically cross-resistant in patients with advanced breast cancer.

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References

  1. Kallio S, Kangas L, Blanco G, Johansson R, Karjalainen A, Perilä M, Piippo I, Sundquist H, Södervall M, Toivola R: A new triphenylethylene compound, Fc-1157a. I. Hormonal effects. Cancer Chemother Pharmacol 17: 103–108, 1986

    Google Scholar 

  2. Kangas L, Nieminen AL, Blanco G, Grönroos M, Kallio S, Karjalainen A, Perilä M, Södervall M, Toivola R: A new triphenylethylene compound, Fc-1157a. II. Antitumor effects. Cancer Chemother Pharmacol 17: 109–113, 1986

    Google Scholar 

  3. Ebbs SR, Roberts JV, Baum M: Alternative mechanism of action of ‘antiestrogens’ in breast cancer. Lancet ii: 621, 1987

    Google Scholar 

  4. Kivinen S, Mäepää J: Effect of toremifene on clinical, hematological and hormonal parameters in different dose levels: phase I study. Proc 14th International Cancer Congress Budapest, 778 (A 2994), 1986

  5. Valavaara R, Pyrhönen S, Heikkinen M, Rissanen P, Blanco G, Thölix E, Nordman E, Taskinen P, Holsti L, Hajba A: Toremifene, a new antiestrogenic compound, for treatment of advanced breast cancer. Phase II study. Eur J Cancer Clin Oncol 24: 785–790, 1988

    Google Scholar 

  6. Modig H, Borgström S, Nilsson I, Westman G: Phase II clinical study of Toremifene in patients with metastatic breast cancer. J Steroid Biochem 36: 235–236, 1990

    Google Scholar 

  7. Gundersen S: Toremifene, a new antiestrogenic compound in the treatment of metastatic mammary cancer. A phase II study. J Steroid Biochem 36: 233–234, 1990

    Google Scholar 

  8. Hietanen T, Baltina D, Johansson R, Numminen S, Hakala T, Helle L, Valavaara R: High dose toremifene (240mg daily) is effective as first line hormonal treatment in advanced breast cancer. An ongoing phase II multicenter Finnish-Latvian cooperative study. Breast Cancer Res Treat 16 (suppl 1): S 37–40, 1990

    Google Scholar 

  9. Pyrhönen S, Valavaara R, Hajba A: High dose toremifene therapy in tamoxifen failed patients with breast cancer. Breast Cancer Res Treat 14: 138 (A 21), 1989

    Google Scholar 

  10. Tormey DC, Simon RM, Lippman ME,et al.: Evaluation of tamoxifen dose in advanced breast cancer. A progress report. Cancer Treat Rep 60: 1451–1459, 1976

    Google Scholar 

  11. Manni A, Arafah BM: Tamoxifen-induced remission in breast cancer by escalating the dose to 40mg daily after progression on 20mg daily. Cancer 48: 873–875, 1981

    Google Scholar 

  12. WHO Handbook for Reporting Results of Cancer Treatment. WHO, Geneva, 1979

  13. Andersen J, Ørntoft TF, Poulsen HS: Immunohistochemical demonstration of estrogen receptors in formalin-fixed, paraffin-embedded human breast cancer tissue by use of a monoclonal antibody to ER. J Histochem Cytochem 36: 1553–1560, 1988

    Google Scholar 

  14. Thorpe SM, Poulsen HS, Pedersen KO, Rose C: Impact of standardization of estrogen and progesterone receptor assays of breast cancer biopsies in Denmark. Eur J Cancer Clin Oncol 24: 1263–1269, 1988

    Google Scholar 

  15. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG: Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35: 1–39, 1977

    Google Scholar 

  16. Pyrhönen S, Valavaara R, Hajba A: High dose toremifene in advanced breast cancer resistant to or relapsed with tamoxifen treatment. J Cancer Res Clin Oncol 16: 396, 1990

    Google Scholar 

  17. Pyrhönen S: Phase III studies of toremifene in metastatic breast cancer. Breast Cancer Res Treat 16 (Suppl): S41–46, 1990

    Google Scholar 

  18. Mehta CR, Cain KC: Charts for the early stopping of pilot studies. J Clin Oncol 2: 676–682, 1984

    Google Scholar 

  19. Modig H, Borgström S, Nilsson I, Westman G: Phase II clinical study of high-dose toremifene in patients with advanced breast cancer. J Steroid Biochem 36: 237–238, 1990

    Google Scholar 

  20. Vogel CL, Green MR, Jones SE, Harry D, Shemano I: Phase II trial of toremifene, a new anti-estrogen, in patients failing tamoxifen. Proc Am Soc Clin Oncol 10: 72, 1991

    Google Scholar 

  21. Jönsson PE, Malmberg M, Bergljung L, Ingvar C, Ericsson M, Ryden S, Nilsson I, Terje IJ: Phase II study of high dose toremifene in advanced breast cancer progressing during tamoxifen treatment. Anticancer Res 11: 873–76, 1991

    Google Scholar 

  22. Hamm JT, Tormey DC, Kohler PC, Haller D, Green M, Shemano I: Phase I study of toremifene in patients with advanced cancer. J Clin Oncol 9: 2036–2041, 1991

    Google Scholar 

  23. Fletcher WS: Endocrine manipulation in advanced breast cancer. Advances in Breast and Endocrine Surgery. Year Book Medical Publishers, Chicago, 1986, pp 193–204

    Google Scholar 

  24. Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards II F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM: Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis. A phase III trial of the Piedmont Oncology Association. J Clin Oncol 7: 1098–1106, 1988

    Google Scholar 

  25. Rose C, Mouridsen HT: Endocrine therapy of advanced breast cancer. Acta Oncol 27: 721–728, 1988

    Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark

    Lars E. Stenbygaard, Jørn Herrstedt, Karsten R. Svendsen, Svend Aa. Engelholm & Per Dombernowsky

  2. Department of Internal Medicine C, Bispebjerg Hospital, University of Copenhagen, DK-2400, Copenhagen, Denmark

    Jane F. Thomsen

Authors
  1. Lars E. Stenbygaard
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  2. Jørn Herrstedt
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  3. Jane F. Thomsen
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  4. Karsten R. Svendsen
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  5. Svend Aa. Engelholm
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  6. Per Dombernowsky
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Stenbygaard, L.E., Herrstedt, J., Thomsen, J.F. et al. Toremifene and tamoxifen in advanced breast cancer - a double-blind cross-over trial. Breast Cancer Res Tr 25, 57–63 (1993). https://doi.org/10.1007/BF00662401

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