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Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor

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Abstract

Background

Aromatase inhibitors (AIs) have been employed as adjuvant therapy or as treatment for recurrent cases. However, when AI treatment fails, it is unclear which endocrine therapy is the most appropriate to introduce at this point and how effective it will be. In this study, we investigated the efficacy and safety of toremifene (TOR, Fareston®), a selective estrogen receptor modulator (SERM).

Methods

Patients with recurrent or advanced breast cancer who had measurable or evaluable lesions, and were diagnosed as having progressive disease during AI treatment and subsequently given TOR at 120 mg/day (TOR120) as endocrine therapy were selected and analyzed retrospectively in relation to their medical history.

Results

Of a total of 83 cases examined, 80 were evaluable. The objective response rate (ORR) was 15.0% (12/80), the clinical benefit (CB) rate was 45.0% (36/80), and median time to failure (TTF) was 7.8 months. TOR120 was also effective in the progressive disease cases relapsed on AI treatment. When TOR120 was used, as a first-, second- or third-line treatment, the CB rate was 57% (32/56); this fell to 17% (4/24) when TOR120 was used as a fourth-line or later treatment. There was no response in the five estrogen receptor (ER)-negative cases, compared with an ORR of 15% (10/67) in ER-positive cases. In cases with a human epidermal growth factor receptor 2 (HER2) score of 0, 1+, and 2+, the ORR was 11% (7/61), while there was no response in the five cases with scores of 3+. TOR120 was effective in cases previously treated with tamoxifen (TAM), with an ORR and CB rate of 12 and 29%, respectively. The last AI used was anastrozole in 30 cases and examestane in 46; the response rates to TOR120 were similar in both groups. With regard to adverse effects, hot flushes and/or night sweating was observed in 10 and 12 cases, respectively, but all of them were categorized as grade 1, and the treatment was rated excellent in acceptability.

Conclusions

TOR120 was rated excellent in acceptability, and high efficacy was observed when it was used up to third-line treatment for AI-failure cases, although this study may show some selection bias because of the retrospective study. In addition, it was also considered effective for TAM-failure cases.

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Conflict of interest statement

Honoraria: Iwase H, AstraZenecea, Pfizer, Chugai-Roche, Takeda, Novartis; Masuda N, Pfizer, Bristol-Myers Squibb, Research Fund: Iwase H, AstraZeneca, Pfizer, Chugai-Roche, Takeda.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Yutaka Yamamoto & Hirotaka Iwase

  2. Department of Surgery, Osaka National Hospital, Osaka, Japan

    Norikazu Masuda

  3. Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan

    Tohru Ohtake

  4. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate, School of Medical Sciences, Nagoya, Japan

    Hiroko Yamashita

  5. Department of Clinical Trials and Research, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

    Shigehira Saji

  6. Department of Surgery, Northern Fukushima Medical Center, Fukushima, Japan

    Izo Kimijima

  7. Department of Surgery, Fukui Saiseikai Hospital, Fukui, Japan

    Yoshio Kasahara

  8. Department of Surgery, Yokohama City University Medical Center, Yokohama, Japan

    Takashi Ishikawa

  9. Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya, Japan

    Masataka Sawaki

  10. Department of Surgery, Jichi Medical University Hospital, Shimotuke, Japan

    Yasuo Hozumi

Authors
  1. Yutaka Yamamoto
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  2. Norikazu Masuda
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  3. Tohru Ohtake
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  4. Hiroko Yamashita
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  7. Yoshio Kasahara
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  8. Takashi Ishikawa
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  9. Masataka Sawaki
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  10. Yasuo Hozumi
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  11. Hirotaka Iwase
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Corresponding author

Correspondence to Hirotaka Iwase.

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Yamamoto, Y., Masuda, N., Ohtake, T. et al. Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor. Breast Cancer 17, 254–260 (2010). https://doi.org/10.1007/s12282-009-0148-2

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  • DOI: https://doi.org/10.1007/s12282-009-0148-2

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