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1.
BMC Cancer ; 20(1): 663, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677982

RESUMO

BACKGROUND: Toremifene (TOR) is a selective oestrogen receptor modulator (SERM) and has comparable efficacy to that of tamoxifen (TAM) in breast cancer patients. Herein, we compared the safety of TOR to that of TAM in the adjuvant treatment of premenopausal breast cancer. METHODS: This was a prospective randomized and open-label clinical study. Premenopausal patients with hormonal receptor (HR)-positive early breast cancer were randomly assigned (1:1) to receive TOR) or TAM treatment. The follow-up period was 1 year. The primary end point was the incidence of ovarian cysts, and secondary end points were the incidence of endometrial thickening, changes in female hormones, the incidence of fatty liver, changes in the modified Kupperman index (mKMI) and changes in quality of life. RESULTS: There were 92 patients in the final analysis. The incidences of ovarian cysts were 42.6% in the TOR group and 51.1% in the TAM group (p = 0.441). Forty-one patients (87.2%) in the TOR group and 36 patients (80.0%) in the TAM group experienced endometrial thickening (p = 0.348). The proportions of patients with fatty liver were 31.9% in the TOR group and 26.7% in the TAM group (p = 0.581). No significant differences in the mKMI or quality of life were observed between the two groups. CONCLUSIONS: TOR and TAM have similar side effects on the female genital system and quality of life in premenopausal early breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02344940. Registered 26 January 2015 (retrospectively registered).


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fígado Gorduroso/epidemiologia , Cistos Ovarianos/epidemiologia , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Adulto , Antineoplásicos Hormonais/administração & dosagem , Mama/patologia , Neoplasias da Mama/patologia , Endométrio/efeitos dos fármacos , Fígado Gorduroso/induzido quimicamente , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Cistos Ovarianos/induzido quimicamente , Pré-Menopausa , Estudos Prospectivos , Qualidade de Vida , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Toremifeno/administração & dosagem , Toremifeno/efeitos adversos
2.
Breast Cancer ; 26(5): 535-543, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30734152

RESUMO

BACKGROUND: An association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. The efficacy of TAM dose escalation appears limited in poor TAM metabolizers. Since the chlorine atom on the side chain of toremifene (TOR) prevents 4-hydroxylation by CYP2D6, its contribution to active conversion of TOR is minor. We examined the role of TOR and its dose escalation among poor TAM metabolizers. METHODS: The pharmacokinetics (PK) and pharmacogenomics (PGx) of TAM and TOR were studied. Correlation between PK and CYP2D6 inhibitor use, smoking status, and PGx were examined by regression analysis. For patients showing low endoxifen levels, an intra-patient dose escalation of TOR was conducted, and TOR was increased from 40 to 120 mg for ≥ 24 weeks with PK sampling. Total activity was calculated as the sum of the concentration of each active metabolite adjusted by their respective in vitro activities. RESULTS: Fifty and 11 of the 273 participating patients had endoxifen levels < 15 and < 7.5 ng/mL, respectively. The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Smoking status (p = 0.07) and the CYP2C19 phenotype (p = 0.07), but not the CYP2D6 genotype (p = 0.61), showed marginally significant effects on TOR activity. TOR activity increased significantly with dose escalation, even among poor TAM metabolizers, and was maintained for ≥ 24 weeks. CONCLUSION: TOR might be a valid alternative to TAM in patients predicted to be poor TAM metabolizers.


Assuntos
Neoplasias da Mama/metabolismo , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Genótipo , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Tamoxifeno/análogos & derivados , Toremifeno/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Inibidores do Citocromo P-450 CYP2D6/uso terapêutico , Feminino , Fogachos/etiologia , Humanos , Hidroxilação , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Fumar , Tamoxifeno/análise , Toremifeno/administração & dosagem , Toremifeno/efeitos adversos , Toremifeno/uso terapêutico
3.
BMC Ophthalmol ; 19(1): 267, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888549

RESUMO

BACKGROUND: The relationship between anti-estrogen drugs and macular telangiectasia type 2 (MacTel-2) remains unknown. Here we report a case with anti-estrogen maculopathy resembling MacTel-2 with improved visual function and macular morphology following cessation of anti-estrogen drugs. CASE PRESENTATION: A 53-year-old woman presented with a 5-month history of central vision loss and anorthopia in both eyes. She had received oral tamoxifen followed by toremifene for 69 months. Funduscopy, fluorescein angiography, and optical coherence tomography (OCT) revealed MacTel-2-like findings OU. Fundus autofluorescence (FAF) showed hyper-autofluorescence at the fovea OU. Visual acuity, macular morphology on OCT, and FAF findings gradually improved after cessation of anti-estrogen drugs. CONCLUSIONS: In the present case, visual acuity, macular morphology, and impairment of the retinal pigment epithelium (RPE) improved following cessation of anti-estrogen drugs, suggesting the relationship between retinal toxicity of anti-estrogen drugs and the development of MacTel-2-like findings. From these results and the previous observations, toxicity of both photoreceptor and RPE cells caused by anti-estrogen drugs may contribute to the development of anti-estrogen maculopathy similar to MacTel-2.


Assuntos
Antagonistas de Estrogênios/efeitos adversos , Retina/patologia , Telangiectasia Retiniana/induzido quimicamente , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos , Acuidade Visual/fisiologia , Suspensão de Tratamento , Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Angiofluoresceinografia , Humanos , Pessoa de Meia-Idade , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/fisiopatologia , Tamoxifeno/uso terapêutico , Tomografia de Coerência Óptica , Toremifeno/uso terapêutico
4.
Cancer Chemother Pharmacol ; 81(2): 269-275, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29196963

RESUMO

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1-2, node metastases (n = 0-3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Letrozol/efeitos adversos , Lipídeos/sangue , Toremifeno/efeitos adversos , Idoso , Fosfatase Alcalina/sangue , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante , Colesterol/sangue , LDL-Colesterol/sangue , Colágeno Tipo I/sangue , Feminino , Humanos , Letrozol/uso terapêutico , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Toremifeno/uso terapêutico
5.
Breast ; 28: 67-72, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27240168

RESUMO

BACKGROUND AND AIM: The aim of this study was to identify the effect of selective estrogen receptor modulator (SERM) on non-alcoholic fatty liver disease (NAFLD) in Asian women. METHODS: We retrospectively evaluated fatty liver development and/or serum alanine aminotransferase (ALT) elevation during SERM treatment in 1061 women who were diagnosed and treated with breast cancer in 2005 at Asan Medical Center. RESULTS: 45 of 618 SERM-treated patients with normal ALT at baseline experienced ALT elevation during SERM treatment. Among the 112 SERM-treated patients who underwent liver imaging test, fatty liver was observed in 47 and both fatty liver and ALT elevation developed in 16 of 102 SERM-treated patients with normal baseline ALT. The cumulative rates of ALT elevation (10.7 vs. 4.3%; P = 0.002), fatty liver (48.5 vs. 20.9%; P < 0.001), and both fatty liver and ALT elevation (17.7 vs. 7.1%; P = 0.02) at 60 months were significantly higher in the SERM group than non-SERM group. By multivariate analysis, SERM treatment increased the risk of ALT elevation (hazard ratio [HR], 2.20; P = 0.01), fatty liver development (HR, 3.59; P < 0.001), and both fatty liver and ALT elevation (HR, 4.98; P = 0.01). After discontinuation of SERM, elevated serum ALT normalized in 39 (92.9%) and there were no instances of liver-related death or progression to liver cirrhosis in patients who experienced fatty liver or ALT elevation. CONCLUSIONS: Although SERM treatment is significantly associated with NAFLD in Asian women, considering the tolerability and reversibility of NAFLD induced by SERM, it can be continued with liver function monitoring in relevant patients.


Assuntos
Alanina Transaminase/sangue , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fígado Gorduroso/induzido quimicamente , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos , Adulto , Idoso , Fígado Gorduroso/sangue , Feminino , Humanos , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Suspensão de Tratamento
6.
Eur J Cancer ; 51(18): 2800-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26602014

RESUMO

INTRODUCTION: Many patients affected by desmoid-type fibromatosis (DF) are treated with a course of hormonal therapy as front line. So far, tamoxifene has been the preferred choice. Toremifene is an anti-oestrogen agent, but possible further mechanisms of action in desmoids are related to its role in regulation of transforming growth factor-beta and ß-catenin pathways. MATERIAL AND METHODS: We retrospectively reviewed all patients treated with toremifene between 2005 and 2012 at a reference institution. Indication to toremifene was radiologically progressive disease and/or symptomatic deterioration. Progression-free survival (PFS), clinical benefit (CB) and safety profile were analysed. RESULTS: Forty-four patients were treated with toremifene 180 mg daily, 20 for radiological progression, 16 for pain and 8 for both. In 28 patients, toremifene was offered as front-line therapy, while in 11 after tamoxifen failure. PFS was 89.6% at 2 years. According to Response Evaluation Criteria in Solid Tumours, partial response, stable disease and disease progression were observed in 25%, 65% and 10% of the patients, respectively. Symptomatic relief was obtained in 75% of patients. Median time to response was 4 months. Overall CB was 86%. Adverse events G≥2 according to National Cancer Institute Common Toxicity Criteria were recorded in ten patients. DISCUSSION: Present series provides evidence to make toremifene an option in patients with DF, even after failure on different hormonal agents. A prospective trial is ongoing to confirm these results.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Toremifeno/uso terapêutico , Adulto , Antineoplásicos Hormonais/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/patologia , Humanos , Itália , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/mortalidade , Neoplasias Hormônio-Dependentes/patologia , Estudos Retrospectivos , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Fatores de Tempo , Toremifeno/efeitos adversos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 94(40): e1718, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26448028

RESUMO

Selective estrogen receptor modulator (SERM)-associated nonalcoholic fatty liver disease (NAFLD) might be related to treatment efficacy in patients with breast cancer because of circulating estrogen antagonism. The aim of the study was to investigate the relationship between NAFLD and survival outcomes in patients with breast cancer who were treated with tamoxifen or toremifene. This single-center, retrospective, cohort study included 785 eligible patients who received tamoxifen or toremifene, after curative resection for breast cancer, at the Sun Yat-sen University Cancer Center between January 2005 and December 2009. Data were extracted from patient medical records. All patients underwent abdominal ultrasonography, at least once, at baseline and at the annual follow-up. Patients who were diagnosed with NAFLD on ultrasonography were classified into the NAFLD or the non-NAFLD arm at the 3-year follow-up visit. Univariate and multivariate Cox regression analyses were conducted to evaluate any associations between NAFLD and disease-free survival (DFS) or overall survival (OS). One hundred fifty-eight patients were diagnosed with NAFLD. Patients who developed NAFLD had better DFS and OS compared with those who did not. Univariate analyses revealed that the 5-year DFS rates were 91.56% and 85.01% for the NAFLD and non-NAFLD arms, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.37-0.96; log-rank P = 0.032). The 5-year OS rates were 96.64% and 93.31% for the NAFLD and non-NAFLD arms, respectively (HR, 0.39; 95% CI, 0.16-0.99; log-rank P = 0.039). Multivariate analysis revealed that NAFLD was an independent prognostic factor for DFS, improving the DFS rate by 41% compared with that in the non-NAFLD arm (HR, 0.59; 95% CI, 0.36-0.96; P = 0.033). SERM-associated NAFLD was independently associated with improved DFS and might be useful for predicting treatment responses in breast cancer patients treated with SERMs.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Toremifeno/uso terapêutico , Ultrassonografia
8.
Gan To Kagaku Ryoho ; 42(12): 1809-11, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805180

RESUMO

A 67-year-old woman underwent total mastectomy, postoperative radiation therapy, and adjuvant hormonal therapy more than 9 years 4 months previously. There were no symptoms of recurrence for 3.5 years after completing adjuvant hormonal therapy. A hard mass appeared on the front chest wall and was diagnosed as recurrence of breast cancer histopathologically. A computed tomography (CT) scan revealed multiple metastases in the left side of the chest wall, in the left Level Ⅱ axillary lymph nodes, and in the left lung. The patient was prescribed high-dose tremifene (HD-TOR 120 mg/day). After less than 4 months, she presented with general fatigue and yellow skin, and was admitted with grade 4 hyperbilirubinemia and grade 3 hepatic dysfunction (AST and ALT). CT and magnetic resonance imaging (MRI) showed no abnormal findings in the liver or biliary tract. Drug-induced liver injury (DILI) caused by HD-TOR was suspected and this therapy was discontinued. The liver dysfunction showed a tendency to improve with conservative treatment and the patient was discharged on the 10th day of illness. She had almost recovered after 5.5 months. A liver biopsy, a drug-lymphocyte stimulation test, and other detailed examinations were not performed, but we judged this case to be one of liver failure caused by HD-TOR-induced DILI.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Falência Hepática/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Toremifeno/efeitos adversos , Idoso , Antineoplásicos Hormonais/uso terapêutico , Biópsia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Toremifeno/uso terapêutico
9.
Clin Breast Cancer ; 14(1): 1-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24439786

RESUMO

Endocrine therapy is a cornerstone of medical treatment for estrogen receptor-positive breast cancer. The discovery of selective estrogen receptor modulators (SERMs) > 40 years ago represented a revolutionary advance in the treatment of breast cancer. As a therapeutic class, SERMs have either estrogenic or antiestrogenic activity, depending on the target tissue and the hormonal environment. In breast tissue, SERMs are antiestrogenic, making them a major treatment option for women with hormone-sensitive breast cancer. Toremifene citrate was developed > 20 years ago with the goal of achieving efficacy similar to that of tamoxifen and with an improved safety profile. Although studies to date have not confirmed a clear safety advantage or disadvantage for toremifene, clinical data support the efficacy and safety of toremifene for the treatment of breast cancer in postmenopausal patients. Toremifene also has a pharmacokinetic profile and metabolic pathway different from that of tamoxifen, which may provide a therapeutic advantage in certain patients. In addition, because of the selective estrogenic effects of SERMs in bone and on lipid levels along with a different side effect profile compared with the aromatase inhibitors (AIs), toremifene is a viable option to the AIs for some patients. Despite a number of clinical trials and over 500,000 patient years of use, many oncologists have limited familiarity with toremifene data. This article will examine the rationale for the use of toremifene in the treatment of women with breast cancer and review data from 20 years of clinical experience with this agent.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Toremifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Citocromo P-450 CYP2D6/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Pós-Menopausa , Toremifeno/efeitos adversos
10.
Breast Cancer ; 21(3): 275-83, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-22968626

RESUMO

BACKGROUND: Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. PATIENTS AND METHODS: The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. RESULTS: A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. CONCLUSION: Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Toremifeno/uso terapêutico , Idoso , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos , Resultado do Tratamento
11.
Gan To Kagaku Ryoho ; 40(6): 749-53, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23863651

RESUMO

BACKGROUND: Third-generation aromatase inhibitors(AIs)are now common in adjuvant hormone therapy for breast cancer in postmenopausal women. However, a suitable treatment has yet to be established for patients who develop cancer recurrence during or after adjuvant AI therapy. PATIENTS AND METHODS: This prospective study evaluated the efficacy and safety of 120mg/day toremifene citrate(TOR-120)administered orally to 23 patients with recurrent breast cancer who were receiving or had received adjuvant AI therapy. Primary therapy for recurrence was TOR-120 monotherapy. RESULTS: The response rate was 13. 0%(partial response: three patients), the clinical benefit rate was 78. 3%(partial response: three patients; long-term stable disease: 15 patients), and median time to progression was 8. 1 months. Grade 1 adverse events such as loss of appetite, sweating, flushing and edema face were observed. CONCLUSION: TOR-120 monotherapy was effective and safe as a primary hormone therapy for recurrent breast cancer unresponsive to AIs.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Toremifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Toremifeno/administração & dosagem , Toremifeno/efeitos adversos
12.
J Obstet Gynaecol Res ; 39(1): 424-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22690656

RESUMO

Low-grade endometrial stromal sarcoma (ESS) is a rare neoplasm that is generally estrogen-receptor- and progesterone-receptor-positive and develops in premenopausal women. Although tamoxifen treatment is associated with an increased risk of ESS, the effect of other selective estrogen receptor modulators, including toremifene, on the risk of ESS is not clear. A 61-year-old postmenopausal woman was treated with toremifene as an adjuvant therapy for breast cancer. A cystic mass developed during the treatment, with gradual growth in the uterine myometrium. The patient was treated with hysterectomy and bilateral salpingo-oophorectomy, and the tumor was diagnosed as low-grade ESS (stage IA) with estrogen-receptor and progesterone-receptor. The patient discontinued toremifene and has been progression-free for 21 months. Our data suggest that toremifene might be associated with the development of ESS in certain patients through its estrogen-like effects in the uterus.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Endométrio/induzido quimicamente , Sarcoma do Estroma Endometrial/induzido quimicamente , Toremifeno/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Pós-Menopausa , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/cirurgia , Toremifeno/uso terapêutico
13.
Wien Med Wochenschr ; 162(17-18): 380-5, 2012 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-22875632

RESUMO

Osteoporosis is defined as a continuous loss of bone mineral density accompanied by an increased fracture risk in females and males. A fall of estrogen concentrations at the menopause and the consecutive rapid bone loss are an established pathogenic mechanism in female osteoporosis. Males do not have a menopause equivalent during which significant amounts of bone are lost. Several diseases, therapeutic strategies and nutritional deficiencies may also result in bone loss and reduced bone mineral density. Prostate cancer is the most common visceral malignancy in men. Suppression of endogenous androgen production as a therapeutic tool is commonly used in patients with non-metastatic prostate cancer and is associated with significant bone loss and an increased fracture risk. Androgen deprivation therapy is prescribed both for men with locally advanced or high-risk non-metastatic prostate cancer. Osteoclast inhibition with any of several bisphosphonates improves bone mineral density and reduces fracture risk. Denosumab (a monoclonal antibody against RANK ligand) and toremifene (a selective estrogen receptor modulator) recently have been shown to be effective to reduce vertebral fractures in patients with non-metastatic prostate cancer receiving androgen-deprivation therapy. This overview focuses on cancer-treatment-induced bone loss in patients with non-metastatic prostate cancer.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Osteoporose/induzido quimicamente , Neoplasias da Próstata/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Denosumab , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Estadiamento de Neoplasias , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/prevenção & controle , Neoplasias da Próstata/patologia , Ligante RANK/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Fraturas da Coluna Vertebral/induzido quimicamente , Fraturas da Coluna Vertebral/prevenção & controle , Toremifeno/efeitos adversos , Toremifeno/uso terapêutico
14.
Cochrane Database Syst Rev ; (7): CD008926, 2012 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-22786516

RESUMO

BACKGROUND: Toremifene (TOR) and tamoxifen (TAM) can both be used as treatments for advanced breast cancer. OBJECTIVES: To compare the efficacy and safety of TOR with TAM in patients with advanced breast cancer. SEARCH METHODS: The Cochrane Breast Cancer Group's Specialised Register was searched (1 July 2011) using the codes for "toremifene", "fareston", "tamoxifen, "nolvadex, and "breast cancer". We also searched MEDLINE (via PubMed) (from inception to 1 July 2011), EMBASE (via Ovid) (from inception to 1 July 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2011), and the WHO International Clinical Trials Registry Platform search portal (1 July 2011). In addition, we screened the reference lists of relevant trials or reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared the efficacy and safety, or both of TOR with TAM in women with advanced breast cancer. Trials that provided sufficient data on one of the following items: objective response rate (ORR), time to progression (TTP), overall survival (OS), and adverse events, were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Two review authors independently extracted the following details: first author, publication year, country, years of follow-up, treatment arms, intention-to-treat (ITT) population size, menopausal status of patients, hormone receptor status, response criteria, efficacy and safety outcomes of TOR and TAM arms. Hazard ratios (HR) were derived for time-to-event outcomes, where possible, and response and adverse events were analysed as dichotomous variables. We used a fixed-effect model for meta-analysis unless there was significant between-study heterogeneity. MAIN RESULTS: A total of 2061 patients from seven RCTs were included for final analysis, with 1226 patients in the TOR group and 835 patients in the TAM group. The ORR for the TOR group was 25.8% (316/1226) whereas, the ORR for the TAM group was 26.9% (225/835). The pooled risk ratio (RR) suggested that the ORRs were not statistically different between the two groups (RR 1.02, 95% confidence interval (CI) 0.88 to 1.18, P = 0.83). The median TTP was 6.1 months for the TOR group and 5.8 months for the TAM group. The median OS was 27.8 months for the TOR group and 27.6 months for the TAM group. There were no significant differences in TTP and OS between the two therapeutic groups (for TTP: HR 1.08, 95% CI 0.94 to 1.24; for OS: HR 1.02, 95% CI 0.86 to 1.20). The frequencies of most adverse events were also similar in the two groups, while headache seemed to occur less in the TOR group than in the TAM group (RR 0.14, 95% CI 0.03 to 0.74, P = 0.02). There was no significant heterogeneity between studies in most of the above meta-analyses. Sensitivity analysis did not alter the results. AUTHORS' CONCLUSIONS: TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Toremifeno/uso terapêutico , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos
15.
J Obstet Gynaecol Res ; 38(12): 1379-84, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22612286

RESUMO

The relation between the use of tamoxifen and gynecologic tumors has been documented. In this case, a 58-year-old postmenopausal woman had been treated with tamoxifen for 5 years followed by toremifene for 1.5 years due to the presence of stage II estrogen receptor-positive breast cancer. The patient was found to have a stage Ic granulosa cell tumor of the ovary despite undergoing annual gynecologic examinations. This report presents a case of granulosa cell tumor of the ovary after the long-term use of tamoxifen and toremifene.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Tumor de Células da Granulosa/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Neoplasias Ovarianas/induzido quimicamente , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Tamoxifeno/administração & dosagem , Toremifeno/administração & dosagem
16.
Gan To Kagaku Ryoho ; 39(5): 753-7, 2012 May.
Artigo em Japonês | MEDLINE | ID: mdl-22584326

RESUMO

BACKGROUND: Aromatase inhibitors(AIs)are frequently employed for advanced or metastatic postmenopausal breast cancer as first-line hormone therapy. However, it is unknown which hormonal agent is the most appropriate after AI has failed. PATIENTS AND METHODS: Five hormone-responsive postmenopausal women who used AI as a first-line hormone therapy for advanced or metastatic breast cancer, but AI failed, received high-dose toremifene therapy(HD-TOR: 120mg/day)in our hospital. Efficacy and safety were evaluated. RESULTS: Patients were all-hormone sensitive, and only one case had HER2 overexpression. All patients had received anastrozole(ANA)as first-line hormone therapy. Of a total of 5 cases, 3 were evaluated as partial responses(PR), 1 was a long stable disease(L-SD), and 1 was a progressive disease(PD). The overall response rate (RR)was 60. 0%(3/5 cases)and the clinical benefit rate(CB)was 80. 0%(4/5 cases). Grade 1 dry mouth was observed in one case as an adverse event. CONCLUSIONS: HD-TOR as a second-line therapy is optimal for advanced or metastatic AI resistance postmenopausal breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Toremifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Toremifeno/administração & dosagem , Toremifeno/efeitos adversos , Resultado do Tratamento
17.
BMC Cancer ; 12: 161, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22548922

RESUMO

BACKGROUND: In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. METHODS: Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. RESULTS: Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. CONCLUSION: Toremifene may be a valid and safe alternative to tamoxifen in premenopausal women with endocrine-responsive breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Pré-Menopausa , Tamoxifeno/uso terapêutico , Toremifeno/uso terapêutico , Adulto , Antineoplásicos Hormonais/efeitos adversos , Protocolos Antineoplásicos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos
18.
Expert Opin Drug Metab Toxicol ; 8(4): 505-13, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22356442

RESUMO

INTRODUCTION: Toremifene is a triphenylethylene selective estrogen receptor modulator (SERM) that differs from tamoxifen in a single chloride ion addition on a side chain, resulting in a potentially more favorable toxicity profile. AREAS COVERED: This article reviews the pharmacokinetics of toremifene and its potential use for the treatment of osteoporosis. This article was based on articles found through a literature search containing the terms 'toremifene' and 'SERMs.' EXPERT OPINION: Toremifene can be administered orally with an excellent bioavailability. The overall pharmacokinetic profile is remarkably similar to tamoxifen. Toremifene is highly metabolized in the liver and is eliminated primarily in the feces following enterohepatic circulation. Some of its metabolites retain biological activity. This SERM was approved by the FDA for the treatment of estrogen receptor-positive metastatic breast cancer and is under investigation for its potential skeletal benefits in men on androgen deprivation therapy. Despite the positive preclinical and clinical evidences for the prevention of bone loss and fractures, the chemopreventive effect on prostate cancer remains to be confirmed and an increased risk of venous thromboembolism was evidenced in a large Phase III trial. Thus, additional data are required to establish the full clinical profile of this compound and its potential advantages over antiresorptive agents commonly in use for the treatment of osteoporosis.


Assuntos
Osteoporose/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Toremifeno/farmacocinética , Toremifeno/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Fígado/metabolismo , Masculino , Neoplasias da Próstata/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tromboembolia/induzido quimicamente , Tromboembolia/epidemiologia , Toremifeno/efeitos adversos
19.
Int J Gynecol Cancer ; 22(2): 280-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22228427

RESUMO

OBJECTIVE: Recent studies reveal an association between hormone therapy for breast cancer (BC), such as tamoxifen (TAM) and toremifene (TOR), and uterine carcinosarcoma (UCS). The aim of this study was to investigate the characteristics and prognosis of patients with UCS after BC and hormone therapy. METHODS: Between January 1997 and December 2007, we treated 51 patients with UCS. The medical records of these patients were reviewed, and factors that influenced their survival were retrospectively analyzed using univariate and multivariate analyses. RESULTS: Ten (19.6%) of the 51 patients had a history of BC; 6 (11.8%) had received hormone therapy with TAM or TOR. The characteristics of the patients with UCS were similar regardless of whether they had a history of BC or hormone therapy. On univariate analysis, age greater than 56 years, elevated serum lactate dehydrogenase levels, residual tumors, FIGO (International Federation of Gynecology and Obstetrics) stage higher than stage IIIa, and non-endometrioid carcinomatous components were identified as prognostic factors. On multivariate analysis, in addition to residual tumors, FIGO stage higher than stage IIIa, and non-endometrioid carcinomatous components, a history of BC (relative risk, 0.14), a history of TAM use (relative risk, 15.9), and a history of TOR use (relative risk, 16.9) were also identified as independently significant prognostic factors. CONCLUSIONS: Our data suggest that a history of BC and hormone therapy for BC is a risk factor for developing UCS without obvious impacts on the characteristics of UCS. Both of these factors had statistically significant impacts on the prognosis of patients with UCS. Further studies are necessary to clarify and validate these associations.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Carcinossarcoma/epidemiologia , Tamoxifeno/efeitos adversos , Toremifeno/efeitos adversos , Neoplasias Uterinas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Carcinossarcoma/induzido quimicamente , Carcinossarcoma/complicações , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Neoplasias Uterinas/induzido quimicamente , Neoplasias Uterinas/complicações
20.
Gan To Kagaku Ryoho ; 38(7): 1123-6, 2011 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-21772095

RESUMO

Aromatase inhibitors (AI) have largely replaced tamoxifen as the first-line of treatment for postmenopausal women with advanced or metastatic hormone-receptor-positive breast cancer. However, there is no established strategy for treating AI refractory cases. In this study, we investigated the efficacy of high-dose Toremifene therapy (HD-TOR). From January 2001 through April 2010, nineteen patients received 120 mg of TOR daily. The overall response rate was 36.8% (CR; 1, PR; 6), and the clinical benefit was 47.4%. The clinical benefit rate to each of the metastatic organs were: lung, 42.9%; bone, 13%; liver, 25%; and lymph node, 40%. A higher clinical benefit rate was observed in lung or lymph node metastases. The clinical benefit rate of HD-TOR as first to third-line therapy was 50%, which was more effective than that of fourth-line therapy. Our data suggests that HD-TOR may be one of the effective treatment strategies for patients with AI refractory advanced or metastatic hormone receptor-positive breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Toremifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Recidiva , Estudos Retrospectivos , Toremifeno/administração & dosagem , Toremifeno/efeitos adversos
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