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

Abstract

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). 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. 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. 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.