Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase II study was undertaken to assess the effect of CAF plus depo-buserelin, as first-line treatment, in premenopausal women with breast cancer. Of 66 patients entered 60 are eligible and evaluable; their median age was 45, estrogen receptor (ER) was positive in 9, negative in 11 and unknown in 40. The median disease free interval (DFI) was 11 months. Metastatic sites were visceral in 14, bone in 34 and soft tissue in 37. Twenty-nine patients had metastatic disease of one site, while 31 had 2-4 sites. An objective response of 82% was documented (29 complete responders and 20 partial responders). Median time to treatment failure was 11.5 months and median survival 37 months. Most commonly encountered side effects attributable to CAF were alopecia, nausea and vomiting, leucopenia and thrombocytopenia. Side effects attributable to buserelin were hot flashes. After one cycle baseline mean serum estradiol fell from premenopausal levels to postmenopausal levels. This study showed that CAF plus buserelin is well tolerated, with a very high response rate in selected premenopausal patients with advanced breast cancer.
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PMID:Cyclophosphamide, doxorubicin and fluorouracil (CAF) plus depo-buserelin in the treatment of premenopausal women with metastatic breast cancer. 128 48

Androcur 50 was administered as monotherapy (n = 73) or as combined therapy with LH-RH agonists (n = 130) in 203 patients during a 6 month period. Eighty two patients had a local invasive disease, 119 had metastatic disease and 2 had a tumor confined to the prostate. Quality of life could be evaluated in 164 patients considered as valid cases for efficacy analysis. General well being improved in 41% of the patients, appetite was better in 34% of the patients and weight increased in 36%. Pain due to metastatic disease decreased or stabilised in 96% of the patients. Of the 203 patients, 8 patients had objective metastatic progression which led to death in one patient. The incidence of side effects observed in all 203 is as follows: 9% gynaecomastia, 6.5% gastro-intestinal disorders. Hot flushes were reported in 2% of the patients in the monotherapy and in 13% of the patients in the combined treatment. This open not controlled trial shows that the use of Androcur 50 in monotherapy or in combined treatment is an effective drug for prostatic carcinoma, improves quality of life and is generally well tolerated.
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PMID:Androcur 50 in the treatment of prostatic carcinoma. Belgian multicentric study with the participation of 30 urologists. 819 33

Toremifene is a chlorinated tamoxifen analogue that is indicated for the treatment of postmenopausal hormone-dependent breast cancer. It competes with estradiol for estrogen receptors and has growth-inhibitory effects on MCF-7 breast cancer cells. At concentrations < 10(-6) mol/L, this growth inhibition can be reversed by estradiol, but at higher concentrations toremifene is cytotoxic. In dimethylbenzanthracene (DMBA)-induced mammary cancer in rats, toremifene has been shown to decrease the number of new tumours and to inhibit the growth of existing tumours. Toremifene causes growth inhibition by suppressing mitosis and inducing apoptosis. The mechanism by which these events occur may involve the induction of transforming growth factor-beta 1 and inhibition of insulin-like growth factor-1 (mecasermin). Toremifene is primarily an antiestrogen, but it has some estrogen agonist properties in postmenopausal women. The latter are reflected by the fall in luteinising hormone and follicle-stimulating hormone levels and the rise in sex hormone-binding globulin levels that are associated with its use in most women. After estrogen priming, toremifene 68mg administered orally has been found to exert a similar antiestrogenic effect on the vaginal epithelium in postmenopausal women as tamoxifen 60mg. The half-life of toremifene in plasma is 5 days, and the drug is > 99% bound to plasma proteins. The main metabolites of toremifene are N-demethyl-toremifene and deaminohydroxy-toremifene. Altered liver, but not kidney, function affects the pharmacokinetics of toremifene. Toremifene 60mg daily is as effective as tamoxifen 20mg daily in the treatment of postmenopausal hormone-dependent breast cancer, producing a response in about 50% of patients. Soft tissue and visceral metastases respond better to toremifene than bone metastases. Most of the adverse effects of toremifene are related to its activity at estrogen receptors and include hot flashes, vaginal discharge and nausea. Although toremifene decreases antithrombin III levels slightly, the incidence of thromboembolic complications is low. Thus far, no carcinogenic effects have been noted in humans, and preclinical data are mostly reassuring. Toremifene has favourable effects on serum lipids, and thus has potential in preventing coronary heart disease. Although toremifene is somewhat more expensive to use than tamoxifen, toremifene is an effective and well tolerated alternative to tamoxifen in the treatment of postmenopausal women with hormone-dependent breast cancer. No formal pharmacoeconomic comparisons of toremifene and tamoxifen have yet been published. Toremifene is potentially safer than tamoxifen in relation to carcinogenic effects and effects on serum lipids.
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PMID:Toremifene in postmenopausal breast cancer. Efficacy, safety and cost. 934 56

Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex((R)), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.
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PMID:FDA drug approval summaries: fulvestrant. 1249 Jul 35

Aromatase inhibitors and inactivators are playing an increasing greater role in breast cancer treatment. Exemestane, a highly specific, steroidal aromatase inactivator, is the newest agent in this class. The drug is highly specific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic breast cancer who have failed one or more previous hormonal therapies. Exemestane 25 mg/day slows disease progression and reduces tumour-related signs and symptoms and the drug exhibits a partial lack of cross-resistance with the non-steroidal aromatase inhibitors. Response rates to exemestane of 14% to 29% were observed including patients with visceral metastases, who have historically proven difficult to treat. In a large phase III trial, exemestane was found to be superior to megestrol acetate with respect to time to progression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and treatment-related discontinuations are rare. In conclusion, exemestane represents a novel and interesting drug for the treatment of advanced breast cancer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention.
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PMID:Exemestane: a review of its clinical efficacy and safety. 1496 85

The use of androgen deprivation therapy (ADT) to treat prostate cancer has favorably impacted outcomes for men with prostate cancer. Androgen deprivation therapy is effective in reducing painful bony metastases and soft tissue visceral disease in advanced-stage prostate cancer. The use of ADT has expanded beyond the metastatic setting and can also be used as adjuvant therapy for patients with locally advanced prostate cancer who received surgery or localized radiation therapy. Luteinizing hormone-releasing hormone agonists are the most common medical therapy used to deprive men of androgen production. Despite the beneficial effects that ADT has on prostate cancer, ADT causes side effects that can impair quality of life. This article will review the impact and treatment of hot flashes in men treated for prostate cancer.
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PMID:Management of hot flashes in men with prostate cancer being treated with androgen deprivation therapy. 1863 64

Testicular carcinoid tumors are rare with only limited studies. We identified 29 primary testicular carcinoid cases from 7 academic institutions. Patients ranged in age from 12 to 65 years old (mean 36). The most common presenting symptom was the sole finding of either a testicular mass or swelling seen in 15/24 cases with available information. The next most common mode of presentation was as an incidental finding seen in 6 cases. Two patients had carcinoid syndrome including diarrhea, hot flashes, and palpitations. Nineteen were pure carcinoid tumors, 3 were associated with cystic teratoma, 2 with cysts lacking epithelial lining, 4 with epidermoid cyst, and 1 with dermoid cyst. The mean size was 2.5 cm. All 29 primary carcinoids lacked associated intratubular germ cell neoplasia, unclassified type. Mitotic figures were rare in primary carcinoid tumors with only 3 cases showing more than 2 per 10 HPF; necrosis was found in only 1 case. Random scattered mild to moderate nuclear atypia was seen in 12/29 cases. Of the 28 cases found premortem, treatment included focal excision in 3 patients and radical orchiectomy in 25 patients. Follow-up, available in 24 cases, ranged from 1 to 228 months (mean 52.7 mo); of the 20 patients with testicular typical carcinoid tumors found premortem, all were alive at last follow-up without recurrences or metastases. Of the 4 patients with a primary atypical carcinoid tumor, 1 at the time of diagnosis had retroperitoneal and lung metastases who after chemotherapy underwent resection of the retroperitoneal tumor showing metastatic yolk sac tumor and embryonal carcinoma. After resection, serum AFP levels remained elevated and the patient is scheduled for salvage chemotherapy and bone marrow transplant. The other 2 patients with atypical carcinoid and follow-up had no evidence of disease at 68 and 114 months. Most primary carcinoid tumors of the testis have a benign clinical course even if associated with epidermoid/dermoid cysts, or histologically mature teratoma. However, lesions with the morphology of atypical carcinoid can occasionally exhibit metastatic spread.
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PMID:Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases. 2035 89

Among men treated with prostatectomy or radiation therapy for localized prostate cancer, the state of an increasing prostate-specific antigen (PSA) level is known as biochemical recurrence (BCR). BCR can be predictive of the development of subsequent distant metastases and ultimately death, but BCR often predates other signs of clinical progression by several years. Although patients may be concerned about their rising PSA levels, physicians attempting to address patient anxiety must inform them that BCR is not typically associated with imminent death from disease, and that the natural history of biochemical progression may be prolonged. Misinterpretation of the significance of early changes in PSA may cause patients to receive androgen deprivation therapy (ADT) prematurely, especially in settings where the disease is unlikely to impact survival. In addition, knowledge of the morbidities associated with ADT (hot flashes, impotence, sarcopenia, metabolic syndrome, bone loss, and increased risk of vascular disease) has accelerated the search for alternative treatment options for these patients. Clinical trials investigating when and how to best use and supplement hormonal therapies in this patient population are under way, as are trials of novel nonhormonal targeted agents, immunotherapies, natural products, and other pharmaceuticals that have been approved by the US Food and Drug Administration (FDA) for other indications. This review will summarize the acceptable standards of care for the management of biochemically recurrent prostate cancer, and will also outline some novel experimental approaches for the treatment of this disease state.
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PMID:Management of biochemically recurrent prostate cancer after local therapy: evolving standards of care and new directions. 2341 59

Exemestane, a steroidal aromatase inhibitor, is licensed for postmenopausal patients with estrogen receptor (ER)-positive breast cancer as second-line therapy in metastatic disease following antiestrogen failure and as part of sequential adjuvant therapy following initial tamoxifen. This study is a systematic literature review, evaluating exemestane in different clinical settings. The Ovid Medline (1948-2012), Embase (1980-2012), and Web of Science (1899-2012) databases were searched. Forty-two relevant articles covering randomized controlled trials were reviewed for efficacy and safety, and three for adherence. With regard to efficacy in metastatic disease, exemestane is superior to megestrol acetate after progression on tamoxifen. There is evidence for noninferiority to fulvestrant (following a prior aromatase inhibitor) and to nonsteroidal aromatase inhibitors in the first-line setting. Combined use with everolimus is shown to be more efficacious than exemestane alone following previous aromatase inhibitor use. In the adjuvant setting, a switch to exemestane after 2-3 years of tamoxifen is superior to 5 years of tamoxifen. Exemestane is noninferior to 5 years of tamoxifen as upfront therapy, and may have a role as an extended adjuvant therapy. Used as neoadjuvant therapy, increased breast conservation is achievable. As chemoprevention, exemestane significantly reduces the incidence of breast cancer in "at-risk" postmenopausal women. Exemestane is associated with myalgias and arthralgias, as well as reduced bone mineral density and increased risk of fracture, which do not appear to persist at follow-up, with subsequent return to pretreatment values. Compared with tamoxifen, there is a reduced incidence of endometrial changes, thromboembolic events, and hot flashes. Limited evidence shows nonadherence in 23%-32% of patients. Evidence is growing in support of exemestane in all clinical settings. It is generally more efficacious and has a better safety profile than tamoxifen. How it compares with the nonsteroidal aromatase inhibitors remains to be established. Further studies are required on adherence to ensure that maximum benefit is obtained.
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PMID:Long-term efficacy and safety of exemestane in the treatment of breast cancer. 2356 64

Intermittent androgen deprivation is increasingly employed as an alternative to continuous life long androgen deprivation therapy for men with advanced or recurrent prostate cancer. Two recent phase III trials have clarified the benefits of intermittent therapy. In men with non-metastatic disease with PSA recurrence after definitive local therapy, intermittent therapy showed equivalent survival to continuous therapy, with significant improvements in quality of life. Patients on intermittent therapy experience improved bone health, less metabolic and hematologic disturbances, fewer hot flashes, as well as improved sexual function. In men with metastatic disease, the data is less clear. The long-awaited results of SWOG 9324 comparing intermittent to continuous therapy in metastatic disease showed a trend to worse outcome in the patients with 'minimal' metastatic disease, and no difference in those with widespread bone mets. The significance of this observation is in dispute. This review also addresses practical issues in the use intermittent therapy, including patient selection, follow-up and cycling of therapy. The recent results of randomized clinical trials now establish that intermittent androgen deprivation therapy is an approach that should be considered the standard of care for most patients with non-metastatic prostate cancer requiring hormonal therapy.
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PMID:Intermittent versus continuous androgen deprivation therapy in advanced prostate cancer. 2370 95


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