Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toremifene (Fareston)-a novel antiestrogenic drug with a triphenylethylene structure-has been effective in the treatment of postmenopausal breast cancer patients. It is safely administered even in high doses up to 300 mg/day. The purpose of the study was to investigate the effect and tolerability of high dose toremifene in the treatment of patients with advanced renal cell carcinoma (RCC). Thirty six patients started the treatment with toremifene 300 mg/day. There were 26 males and 10 females. Mean age was 56.0 years, range 35-75 years. Nineteen patients were nephrectomized. One patient was not evaluable for response because of too short treatment time. The response rate was 17.1%, including 1 CR (2.9%) lasting for 121 + weeks and 5 PR (14.3%) with the mean duration of 39.8 + weeks. Ten cases of NC (28.6%) had the mean duration of 23.7 weeks. There were no significant differences in response rate when patients with lung metastases only were compared to patients with metastases of other sites with or without lung metastases. Total pain control was achieved in 45% and partial control in 20% of those patients who had pains in the beginning of the treatment. Ten patients (27.8%) had adverse reactions which led to discontinuation of the treatment in one case. It can be concluded that high-dose toremifene is an effective and safe means of palliative treatment in advanced RCC.
 ...
PMID:[Hormone therapy of advanced renal cancer with high-dose toremifene (Fareston)]. 906 93

Toremifene (Fareston)-a novel antiestrogenic drug with a triphenylethylene structure-is effective in the treatment of postmenopausal breast cancer patients. It can be safely given even at high doses of up to 300 mg/day. The purpose of the present study was to investigate the effect and tolerability of high-dose toremifene in the treatment of patients with advanced renal-cell carcinoma (RCC). A total of 36 patients started treatment with toremifene at 300 mg/day, including 26 men and 10 women. Their mean age was 56 years (range 35-75 years). In all, 19 patients were nephrectomized. One patient was not evaluable for response because of insufficient treatment time. The response rate was 17%, including one complete response (CR, 3%) lasting for 121+ weeks and five partial responses (PRs, 14%) with a mean duration of 40+ weeks. Ten cases of no change (NC, 28%) had a mean duration of 24 weeks. There was no significant difference in the response rate when patients with lung metastases alone were compared with patients showing metastases of other sites with or without lung metastases. Total pain control was achieved in 45% of the patients who had pain at the beginning of the treatment, and partial control was attained in 20%. Ten patients (28%) developed adverse reactions, which led to discontinuation of the treatment in one case. Blood samples were taken from 16 patients on days 0, 1, 3, 7, 14, and 28 for drug analyses. The concentration of toremifene and its main metabolites measured in serum were about 1.5 times that detected after a conventional dose of 60 mg/day. It can be concluded that high-dose toremifene is an effective and safe palliative treatment in advanced RCC.
 ...
PMID:High-dose toremifene in advanced renal-cell carcinoma. 911 68

In postmenopausal women, about 65% to 80% of breast cancers contain estrogen receptors (ERs) and 50% to 65%, progesterone receptors (PRs). Receptor-positive breast cancer is somewhat less common in premenopausal patients. Recently, the biochemical dextran-coated charcoal (DCC) assay for ERs has been replaced in many laboratories by immunohistochemical and immunocytochemical methods, which are not disturbed by endogenous estrogen or antiestrogen treatment. Receptors now can also be assayed from fine-needle biopsy and paraffin-embedded tissue specimens. The ER has been shown to be a prognostic factor for overall and disease-free survival in newly diagnosed and relapsed breast cancer. The value of the ER in predicting response to both surgical and medical endocrine treatment of breast cancer has been demonstrated. Ample evidence supports the predictive value of the ER in the treatment of breast cancer with the antiestrogen tamoxifen (Nolvadex). The first studies of a new antiestrogen, toremifene (Fareston), support the value of the ER in predicting breast cancer treatment results.
 ...
PMID:Reliability of estrogen receptors in predicting response to antiestrogens. 916 1

Toremifene (Fareston) is a triphenylethylene derivative structurally similar to tamoxifen (Nolvadex) that was selected for development based on its in vitro activity against breast cancer and its lesser uterotrophic effect than tamoxifen in rat models. In phase I and II studies conducted in several countries, toremifene was well tolerated over a wide range of doses (10 to 680 mg/d). The major side effects were hot flashes, nausea, and vomiting. Toremifene's excretion half-life is 5 days. It produces a modest decline in serum levels of luteinizing hormone, follicle-stimulating hormone, and antithrombin III, as well as an increase in sex hormone-binding globulin levels. In studies in which toremifene was used as first-line therapy in patients with estrogen receptor (ER)-positive or ER-unknown tumors, response rates to doses of 40 to 60 mg/day ranged from 30% to 54%. In two larger studies of patients who had proved refractory to tamoxifen therapy, toremifene produced an objective response rate of 4% to 5%. When patients with stable disease were added to those with objective responses, 27% to 28% of patients were considered to derive clinical benefit from toremifene. The dose range chosen for further study was 40 to 60 mg/d.
 ...
PMID:Phase I and II studies of toremifene. 916 2

Three pivotal phase III trials conducted in North America and Europe served as the basis for the application for approval of toremifene (Fareston) by the FDA. These trials demonstrated that 60 mg/d of toremifene is safe and effective in the treatment of advanced breast cancer in postmenopausal women. The studies also indicated that, on the basis of antitumor efficacy, as well as safety, toremifene is at least equivalent to tamoxifen and may have some long-term advantages.
 ...
PMID:Phase III trials of toremifene vs tamoxifen. 916 3

To compare the efficacy and safety of high doses (200 or 240 mg/d) of toremifene (Fareston) to standard doses (20 or 40 mg/d) of tamoxifen (Nolvadex) in postmenopausal women with estrogen receptor (ER)-positive or ER-unknown advanced breast cancer, we pooled data from two randomized, three-arm clinical trials. Of the 733 patients included in the overview, 369 were randomized to high-dose toremifene and 364, to tamoxifen. At median follow-up of 19 months, disease had progressed in over 70% of the patients. Response rates were 25.2% in the high-dose toremifene arm and 19.8% in the tamoxifen arm (P = .087). The two treatments appeared to be statistically equivalent with respect to risk for disease progression and survival. Reversible SGOT elevation was observed in 26 tamoxifen-treated patients vs 64 high-dose toremifene recipients (P < .001) and nausea in 33 vs 50 patients (P = .085). Reversible corneal keratopathy was diagnosed in two patients on tamoxifen and eight on high-dose toremifene (P = .061). Treatment had to be discontinued in 17.3% of patients in the high-dose toremifene arm and 20.1% in the tamoxifen arm. Discontinuation due to toxicity was rare, and toxicity did not differ significantly between the treatments. Toremifene, in doses up to 240 mg/d, is an effective, safe treatment for postmenopausal women with ER-positive/unknown advanced breast cancer.
 ...
PMID:High-dose toremifene vs tamoxifen in postmenopausal advanced breast cancer. 916 4

In an open phase II study conducted in Finland and Latvia, 73 postmenopausal women were treated with 240 mg of toremifene (Fareston) as first-line therapy for advanced breast cancer. Among the 56 patients evaluable for responses, 59% achieved objective responses [complete response (CR) plus partial response (PR)], 29% showed no change (NC), and 12% had progressive disease (PD). When all treated patients were included, the objective response rate was 47%. Several very long durations of responses up to 86 months and survival durations up to 95 months were observed. In assessable patients, the best objective response rates were seen in those with soft-tissue (74%) and visceral (60%) disease. In 54% of patients with very large inoperable primary cancers, a PR was achieved. Half of patients reported side effects, about 60% of which were mild; 30%, moderate; and 5%, severe. Based on response rate and safety, high-dose toremifene is useful as first-line therapy for advanced breast cancer.
 ...
PMID:Open phase II study of high-dose toremifene as first-line therapy for advanced breast cancer. 916 5

The Finnish Breast Cancer Group (FBCG) started the first multicenter trial of toremifene (Fareston) in the adjuvant setting in 1992. The primary aim of the trial is to compare the efficacy and side effects of toremifene and tamoxifen (Nolvadex) as adjuvant therapies for postmenopausal node-positive breast cancer patients. About 830 patients have been enrolled in the trial to date. An interim analysis of the first 500 patients, performed after a mean follow-up of 18 months, showed no significant difference between toremifene and tamoxifen with regard to efficacy or side effects. The study includes additional protocols aimed at examining some side effects, including ocular problems and the formation of DNA adducts in the endometrium and leukocytes, as well as possible additional benefits, such as effects on lipid levels and bone density. Toremifene also is being studied in two other trials in Europe. These studies, which are being coordinated by the International Breast Cancer Study Group (IBCSG), have enrolled approximately 600 patients to date.
 ...
PMID:Evolving role of toremifene in the adjuvant setting. 916 7

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.
 ...
PMID:Adjuvant trials of toremifene vs tamoxifen: the European experience. 955 87

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.
 ...
PMID:Status of antiestrogen breast cancer prevention trials. 955 88


1 2 Next >>