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Oncology (Williston Park, N.Y.) Mar 1998Toremifene (Fareston) received FDA approval in 1997 for the first-line treatment of postmenopausal women with estrogen receptor (ER)-positive or -unknown metastatic... (Review)
Review
Toremifene (Fareston) received FDA approval in 1997 for the first-line treatment of postmenopausal women with estrogen receptor (ER)-positive or -unknown metastatic breast cancer. Phase II and III trials have demonstrated that first-line therapy with toremifene, 60 mg/d, is as effective and as well tolerated as tamoxifen (Nolvadex), 20 or 40 mg/d, in such patients. To date, phase III trials have failed to show a statistically significant advantage of higher toremifene doses over standard doses of tamoxifen in these women. Studies appeared to indicate minimal efficacy of high toremifene doses in women with ER-negative tumors, but the number of patients studied was small. Although results of some trials of high-dose (240 mg/d) toremifene in tamoxifen-"refractory" patients were negative, other trials that included prolonged (> or = 6 months) stable disease as an indication of clinical benefit yielded positive results.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Estrogen Antagonists; Female; Humans; Neoplasms, Hormone-Dependent; Randomized Controlled Trials as Topic; Receptors, Estrogen; Survival Analysis; Tamoxifen; Toremifene; Treatment Outcome
PubMed: 9556785
DOI: No ID Found -
International Journal of Cancer May 2022CYP2D6 gene polymorphism has a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancer. However, it had never been reported whether...
CYP2D6 gene polymorphism has a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancer. However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. We conducted a retrospective study in breast cancer patients to investigate the impact of CYP2D6 metabolic status on liver dysfunction events, gynecological events and dyslipidemia events. According to CYP2D6*10 (100C → T) genotype, the enrolled patients were further categorized into four cohorts (extensive metabolizers taking tamoxifen [EM + TAM], extensive metabolizers taking toremifene [EM + TOR], intermediate metabolizers taking tamoxifen [IM + TAM], and intermediate metabolizers taking toremifene [IM + TOR]). A total of 192 patients were included in the study, with a median follow-up time of 26.2 months. In EM + TAM cohort, the risks of liver dysfunction events (P = .004) and gynecological events (P = .004) were significantly higher compared to EM + TOR cohort. In IM + TAM cohort, the risks of liver dysfunction events (P = .14) and gynecological events (P = .99) were not significantly different from IM + TOR cohort. A significant decrease of total cholesterol was observed in EM + TAM cohort around 1 year after taking tamoxifen (P < .001). Significant interactions between CYP2D6 metabolic status and endocrine agents were observed in terms of liver dysfunction events (P-interaction = .007) and gynecological events (P-interaction = .026). These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cohort Studies; Cytochrome P-450 CYP2D6; Drug-Related Side Effects and Adverse Reactions; Female; Genotype; Humans; Retrospective Studies; Tamoxifen; Toremifene
PubMed: 34957551
DOI: 10.1002/ijc.33919 -
Oncology (Williston Park, N.Y.) Mar 1998When results from the phase II trials of toremifene (Fareston) and tamoxifen (Nolvadex) in metastatic breast cancer were published, the Finnish Breast Cancer Group began... (Review)
Review
When results from the phase II trials of toremifene (Fareston) and tamoxifen (Nolvadex) in metastatic breast cancer were published, the Finnish Breast Cancer Group began to plan the first trial of toremifene in an adjuvant setting. This multicenter, randomized trial is comparing toremifene (40 mg/d) to tamoxifen (20 mg/d) in postmenopausal lymph node-positive breast cancer patients. Treatment duration is 3 years. About 1,150 of a planned 1,460 patients have been enrolled to date. The International Breast Cancer Study Group is also conducting two adjuvant trials evaluating 5 years of toremifene (60 mg/d) vs tamoxifen (20 mg/d). More than 1,000 patients have been enrolled in these studies to date. The efficacy of toremifene is being explored in all of these trials. In the Finnish trial, additional protocols are evaluating treatment side effects, including the formation of DNA adducts in the endometrium and leukocytes, certain ocular problems, thromboembolic events, and subjective side effects. The effects of toremifene on lipid levels and bone density are also being studied. An interim safety analysis, performed in the Finnish study after 500 patients were enrolled (mean follow-up, 18 months), showed no significant differences between toremifene and tamoxifen in terms of efficacy or side effects. Toremifene seems to be well tolerated and may have additional positive effects. Ongoing trials will soon reveal how beneficial toremifene is in the adjuvant setting and whether it is devoid of the adverse effects observed with tamoxifen.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Estrogen Antagonists; Europe; Female; Humans; Multicenter Studies as Topic; Neoplasms, Hormone-Dependent; Randomized Controlled Trials as Topic; Receptors, Estrogen; Tamoxifen; Toremifene
PubMed: 9556787
DOI: No ID Found -
Endocrinology Oct 2021Cancer-induced skeletal muscle defects show sex-specific differences in severity with men performing poorly compared to women. Hormones and sex chromosomal differences...
Cancer-induced skeletal muscle defects show sex-specific differences in severity with men performing poorly compared to women. Hormones and sex chromosomal differences are suggested to mediate these differences, but the functional skeletal muscle markers to document these differences are unknown. We show that the myogenic microRNA miR-486 is a marker of sex-specific differences in cancer-induced skeletal muscle defects. Cancer-induced loss of circulating miR-486 was more severe in men with bladder, lung, and pancreatic cancers compared to women with the same cancer types. In a syngeneic model of pancreatic cancer, circulating and skeletal muscle loss of miR-486 was more severe in male mice compared to female mice. Estradiol (E2) and the clinically used selective estrogen receptor modulator toremifene increased miR-486 in undifferentiated and differentiated myoblast cell line C2C12 and E2-inducible expression correlated with direct binding of estrogen receptor alpha (ERα) to the regulatory region of the miR-486 gene. E2 and toremifene reduced the actions of cytokines such as myostatin, transforming growth factor β, and tumor necrosis factor α, which mediate cancer-induced skeletal muscle wasting. E2- and toremifene-treated C2C12 myoblast/myotube cells contained elevated levels of active protein kinase B (AKT) with a corresponding decrease in the levels of its negative regulator PTEN, which is a target of miR-486. We propose an ERα:E2-miR-486-AKT signaling axis, which reduces the deleterious effects of cancer-induced cytokines/chemokines on skeletal muscle mass and/or function.
Topics: Animals; Cell Differentiation; Cell Line, Tumor; Estradiol; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Muscle, Skeletal; Muscular Diseases; Myostatin; Neoplasms; Sex Factors; Signal Transduction; Toremifene; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
PubMed: 34265069
DOI: 10.1210/endocr/bqab142 -
Breast Cancer (Tokyo, Japan) Jan 2018In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane, toremifene and tamoxifen. But the optimum regimen remains controversial.
METHODS
PubMed, Cochrane Database and ClinicalTrials.gov were systematically reviewed of abstract for randomized-controlled trials (RCTs) to assess the efficacy of tamoxifen, letrozole, exemestane, anastrozle and toremifene for postmenopausal patients with hormone-receptor positive (HR+), who have not received prior therapy for early stage breast cancer. The outcomes were measured by disease-free survival (DFS) and overall survival (OS). We evaluated relative hazard ratios (HRs) for death of different therapies by combination hazard ratios for death of included trials. The SUCRA values were used to evaluate the rankings of efficacy for these monotherapies.
RESULTS
A total of fourteen studies including 19,517 patients in our research were absorbed and estimated. The superiority of efficacy for DFS were 5-year letrozole and 10-year tamoxifen (SUCRA values 0.743/0.657) in all comparisons. A more efficient SUCRA values for OS were 5-year Exemestane, 5-year letrozole and 10-year tamoxifen (0.756/0.677/0.669).
CONCLUSIONS
Clinically important differences exist between commonly prescribed different adjuvant endocrine monotherapy regimens for both efficacy and acceptability in favor of exemestane and letrozole. 10-year tamoxifen for early breast cancer patients is noninferior to 5-year anastrozle, and might be the best choice where aromatase inhibitors (AIs) are not easy to acquire.
Topics: Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Network Meta-Analysis; Postmenopause; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 28755088
DOI: 10.1007/s12282-017-0794-8 -
Journal of the Endocrine Society Feb 2018Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent...
CONTEXT
Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene.
OBJECTIVE
To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone-ghrelin stimulation. Additionally, effects on IGF-I, its binding proteins, and sex hormone-binding globulin (SHBG) were quantified.
PARTICIPANTS AND DESIGN
Twenty men and 20 women, within an allowable age range of 50 to 80 years, volunteered for this double-blind, placebo-controlled prospective crossover study. Ten-minute blood sampling was done for 10 hours overnight and then for 2 hours after combined GH-releasing hormone-ghrelin injection.
MAIN OUTCOME MEASURES
Pulsatile GH and stimulated GH secretion, and fasting levels of IGF-I, IGF-binding protein (IGFBP)1, IGFBP3, and SHBG.
RESULTS
Toremifene did not enhance pulsatile or stimulated GH secretion, but decreased IGF-I by 20% in men and women. IGFBP3 was unchanged, whereas while IGFBP1 and SHBG increased in both sexes to a similar extent.
CONCLUSIONS
The expected rise in spontaneous and stimulated GH secretion under the diminished negative feedback restraint of powered IGF-I favors a central inhibitory antiestrogenic effect of toremifene. Estrogenic effects of toremifene on the liver were present, as evidenced by increased IGFBP1 and SHBG levels. Men and women responded to this SERM comparably.
PubMed: 29383334
DOI: 10.1210/js.2017-00457 -
Oncology (Williston Park, N.Y.) Mar 1998Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women... (Review)
Review
Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2. Adverse effects of tamoxifen have been identified, including a transient bone loss in premenopausal women and uterine effects, including polyps, cysts, and endometrial cancer, in postmenopausal women. Although the potential benefit of tamoxifen in preventing breast cancer in healthy women is likely to outweight any potential long-term risks, the use of other tamoxifen-like drugs, such as raloxifene (Evista) and toremifene (Fareston) is now being investigated.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Double-Blind Method; Endometrial Neoplasms; Estrogen Antagonists; Female; Genes, BRCA1; Humans; Italy; Neoplasms, Hormone-Dependent; Osteoporosis, Postmenopausal; Piperidines; Raloxifene Hydrochloride; Tamoxifen; Toremifene; United Kingdom; United States
PubMed: 9556788
DOI: No ID Found -
Cancers Jan 2018Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor... (Review)
Review
Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually acquires a lethal phenotype and results in castration-resistant PC (CRPC) during ADT. Therefore, new therapeutic strategies are required in clinical practice. In addition, ARs; estrogen receptors (ERs; ERα and ERβ); and estrogen-related receptors (ERRs; ERRα, ERRβ, and ERRγ) have been reported to be involved in the development or regulation of PC. Recent investigations have revealed the role of associated molecules, such as , , , , , , and of PC, via ERs and ERRs. Selective ER modulators (SERMs) have been developed. Recently, estrogen and androgen blockade (EAB) using a combination of toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC. In the future, the suitability of ADT alone or EAB for individuals may be evaluated by making clinical decisions on the basis of information obtained from RT-PCR, gene-panel, or liquid biopsy to create a "personalized medicine" or "precision medicine". In this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and SERMs as candidates for advanced PC treatment.
PubMed: 29360794
DOI: 10.3390/cancers10020029 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Mar 2022To screen small-molecule antibacterial drugs and investigate the antibacterial effect and mechanism of selective estrogen receptor modulators (SERMs) against .
OBJECTIVES
To screen small-molecule antibacterial drugs and investigate the antibacterial effect and mechanism of selective estrogen receptor modulators (SERMs) against .
METHODS
The minimum inhibitory concentration of 426 Food and Drug Administration (FDA)-approved small-molecule drugs against was determined using the microdilution method, and the target of SERMs acting on was explored by employing a random transposon mutant library.
RESULTS
Among the 426 FDA-approved SERMs, toremiphene, tamoxifen, clomiphene, and raloxifene exhibited excellent antibacterial effects against . Results of mutant library screening showed that the two mutant strains were resistant to clomiphene. The gene sequence of the resistant strains showed that the transposon insertion sites were located in the genes of and .
CONCLUSIONS
SERMs, such as toremifene, tamoxifen, clomiphene, and raloxifene, exerted obvious antibacterial effects on , and their targets may be proteins expressed by and gene.
PubMed: 38597056
DOI: 10.7518/hxkq.2022.02.014 -
Asia-Pacific Journal of Clinical... Apr 2022To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy.
PURPOSE
To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy.
METHODS
Estrogen receptor-positive breast cancer patients were selected and CYP2D6*10 genotypes (C/C, C/T, and T/T) were determined by Sanger sequencing. Patients were divided into tamoxifen, toremifene, or tamoxifen + toremifene groups according to prior therapy. The correlation between CYP2D6*10 genotype and disease-free survival was analyzed.
RESULTS
In total, 293 estrogen receptor-positive breast cancer patients treated with tamoxifen or toremifene between 2008 and 2017 were studied. Median follow-up was 39 months (10-141). Of these, 107 (36.52%), 112 (38.23%), and 74 (25.26%) patients had C/C, C/T, and T/T genotypes, respectively. Genotype was significantly associated with disease-free survival in tamoxifen patients. Patients with C/T and T/T genotypes showed worse disease-free survival than patients with a C/C genotype. Genotype and disease-free survival in toremifene and tamoxifen+toremifene patients were not correlated. Of patients with a C/T genotype, toremifene or tamoxifen+toremifene groups showed better disease-free survival than tamoxifen patients. Although disease-free survival of patients with a T/T genotype in the three groups was not statistically different, tamoxifen patients showed worse disease-free survival. There was no correlation between different treatments and disease-free survival in patients with a C/C genotype. Cox proportional hazard analysis revealed toremifene patients had a better prognosis than tamoxifen patients; toremifene was an independent protective factoremifene for disease-free survival.
CONCLUSIONS
Tamoxifen was less effective in patients with CYP2D6*10 C/T and T/T genotypes. Estrogen receptor-positive breast cancer patients with a CYP2D6*10 mutation genotype have a better prognosis with toremifen than tamoxifen.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; China; Cytochrome P-450 CYP2D6; Female; Genotype; Humans; Prognosis; Receptors, Estrogen; Tamoxifen; Toremifene
PubMed: 34196110
DOI: 10.1111/ajco.13571