Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostatic Carcinoma is known to be a hormonally responsive neoplasm which contains both estrogen and androgen receptors. Sixty-three heavily pretreated patients with Stage D prostatic adenocarcinoma received tamoxifen (Nolvadex) at a dose of 20 mg twice a day. Patients were examined every 4 weeks at which time they also had a white count, hemoglobin and platelet count, acid phosphatase, SMA-12, and recording of the status of their measurable or evaluable disease. If the evaluable disease was metastatic to bone, the relevant x-rays were repeated every 8 weeks. The median age of the patients was 66. The Karnofsky status of the patients for whom this information was known was 40% (6), 45% (1), 50% (1), 60% (8), 70% (11), 80% (6), 90% (5), and 100% (2). Forty-one patients were eligible for response evaluation; the majority had evaluable bone disease. No serious toxicity was encountered; two patients withdrew from the protocol because of nausea and vomiting and one patient had hot flashes. One complete response was seen in measurable nodal disease which is continuing after 13+ months, 1 minor response was seen in evaluable bone disease, and 4 patients had long (more than 10 months) stability of bone disease with subjective improvement. We conclude that although the response rate was low, patient acceptability was excellent and that tamoxifen may warrant further trial in a less heavily pretreated patient population.
 ...
PMID:A phase II study Nolvadex: tamoxifen citrate in the treatment of advanced prostatic adenocarcinoma. 709 Oct 40

The symptomatic postmenopausal woman with breast cancer presents the clinician with a difficult task with respect to hormone replacement therapy (HRT). All of the published meta-analyses have been consistent in showing that there is a slightly increased risk of developing breast cancer in those patients using postmenopausal estrogens for greater than 10 years. However, there have been no published placebo-controlled clinical trials on the effects of HRT in women with a history of breast cancer. Quality of life must be balanced against the theoretical risk of tumor promotion. Assessment of osteoporotic and cardiac risk factors (i.e., smoking, hypertension, family history, hyperlipidemia) should influence the decision. Valid alternatives to estrogen replacement include low-dose progesterones such as Bellergal or vitamin E for hot flashes, and biphosphonates, calcium, anabolic steroids, and calcitonin for osteoporosis.
 ...
PMID:The management of menopausal symptoms in women with breast cancer. 761 Jun 43

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.
 ...
PMID:Androcur 50 in the treatment of prostatic carcinoma. Belgian multicentric study with the participation of 30 urologists. 819 33

Two open-label, multicenter studies were conducted to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide acetate (22.5 mg) administered intramuscularly every 12 weeks to patients with stage D2 prostate cancer. Clinical evaluations were performed every 12 weeks, and serum testosterone levels were monitored biweekly or weekly for 24 weeks. Onset of castrate levels (< or = 50 ng/dL) of testosterone was achieved within 30 days of the initial depot injection in 87 (95%) of the 92 assessable patients enrolled in the two studies. Mean testosterone levels remained well within the castrate range throughout each dosing interval. Two patients experienced a transient escape (testosterone levels > 50 ng/dL on two consecutive determinations). Delay of an injection of up to 2 weeks did not have an effect on testosterone suppression: in 16 patients in whom the depot injection was delayed by 3 to 14 days, testosterone values remained within the castrate range. A favorable objective tumor response (no progression) to treatment occurred in 85% of the patients. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more in 96% and 84% of patients, respectively, with elevated pretreatment values and at least one treatment value. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (59%), pain (27%), and testicular atrophy (21%). The 22.5-mg depot formulation of leuprolide, which acts in a manner similar to the monthly 7.5-mg depot formulation, was shown to be effective and safe in treating patients with advanced prostate cancer.
 ...
PMID:Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer. 887 93

Estrogens play a central role in reproductive physiology. The cellular effects of estrogens are mediated by binding to nuclear receptors (ER) which activate transcription of genes involved in cellular growth control. At least two such receptors, designated ERalpha and ERbeta, mediate these effects in conjunction with a number of coactivators. These receptors can directly interact with other members of the steroid receptor superfamily. A complex cross-talk exists between the estrogen-signaling pathways and the downstream signaling events initiated by growth factors, such as epidermal growth factor and insulin-like growth factors. Estrogens are also a causative factor in the pathogenesis of a variety of neoplastic and non-neoplastic diseases, including breast cancer, endometrial cancer, endometriosis, and uterine fibroids, among others. Antiestrogens, such as tamoxifen, are widely used for the treatment of breast cancer. Tamoxifen produces objective tumor shrinkage in advanced breast cancer, reduces the risk of relapse in women treated for invasive breast cancer, and prevents breast cancer in high-risk women. Although, initially developed as an antiestrogen, tamoxifen can also prevent postmenopausal osteoporosis as well as reduce cholesterol, due to its estrogen-agonist effects. Its estrogen-agonist activity, however, can lead to significant side-effects such as endometrial cancer and thromboembolic phenomena. This has led to the concept of "ideal" selective estrogen receptor modulators (SERMs), drugs that would have the desired, tissue selective, estrogen-agonist or -antagonist effects. Raloxifene is a SERM which has the desirable mixed agonist/antagonist effects of tamoxifen but does not cause uterine stimulation. "Pure" antiestrogens may provide very potent estrogen-antagonist drugs, but are likely to be devoid of beneficial effects on bone and lipids. Future drug development efforts should focus on developing superior SERMs that have a greater efficacy against ER-positive tumors and do not cause hot flashes or thromboembolism, and explore combination strategies to simultaneously target hormone-dependent as well as hormone-independent breast cancer.
 ...
PMID:Antiestrogens--tamoxifen, SERMs and beyond. 1066 80

Endocrine treatment of prostate cancer has been established for more than 5 decades. Focusing on immediate or short-term side effects, bilateral orchidectomy may cause psychological trauma, treatment with oral estrogens is combined with a high risk of severe cardiovascular complications, and the use of LH-RH agonists and antiandrogens as monotherapies or in combination may result in tumor flare, hot flashes, and gynecomastia. In recent years an increasing number of reports on anemia and/or osteoporosis related to endocrine treatment have been published. These side effects are regular and persistent after orchidectomy, or during treatment with LH-RH agonists, and are most often expressed with maximum androgen blockade. In contrast, anemia and/or osteoporosis are not reported with estrogen treatment or the use of nonsteroidal antiandrogens as a monotherapy regimen. Since many prostate cancer patients are treated hormonally for many years, control of Hb levels and bone mineral density before and after initiation of treatment at regular intervals is highly recommended as a standard of care.
 ...
PMID:Potential side-effects of endocrine treatment of long duration in prostate cancer. 1105 92

The demonstration by the National Surgical Adjuvant Breast Project (NSABP) that 5 years of tamoxifen therapy is associated with an approximate 50% reduction in breast cancer incidence in high-risk women was a milestone in breast cancer prevention. Because tamoxifen is associated with increased risk of side-effects such as hot flashes, menstrual abnormalities, uterine cancer, and thromboembolic phenomena, its use will not be advisable or acceptable for all high-risk women. Women over 50 years of age appear to be at highest risk for serious adverse events, such as uterine cancer and thromboembolic phenomena. Individuals in whom tamoxifen-associated breast cancer risk reduction appears to outweigh risk of serious side-effects include women with prior in situ or estrogen receptor (ER)-positive invasive cancer, atypical hyperplasia, and/or women ages 35-49 with a calculated Gail 5-year risk of > or =1.7%, hysterectomized women aged 50 and older with a 5-year Gail risk of > or =2.5%, and nonhysterectomized women aged 50 and older with a 5-year Gail risk of >5.0%. It is not yet clear whether tamoxifen can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation. Raloxifene is a selective ER modulator with less uterine estrogen agonist activity than tamoxifen, and it is hoped that it will result in fewer uterine cancers but will be equally efficacious in reducing the risk of breast cancer. The NSABP is currently conducting a randomized study of tamoxifen versus raloxifene in high-risk postmenopausal women. Approximately one third of invasive cancers are ER negative. Tamoxifen does not reduce the incidence of ER-negative cancers, nor does it appear to be effective in preventing the appearance of one third of ER-positive cancers. Priorities in prevention research are to develop (a) biomarkers to refine short-term risk assessments based on epidemiologic models, (b) biomarkers predictive of response to specific classes of preventive agents, (c) drugs with fewer side-effects and/or effective in ER-negative or ER-positive tamoxifen-resistant precancerous disease, and (d) efficient clinical trial models to assess new agent efficacy. Breast intraepithelial neoplasia (IEN) may be sampled by minimally invasive techniques and is an attractive short-term risk biomarker. Molecular abnormalities observed in IEN may be used to select potential agents for testing/therapy, and modulation of these abnormalities may be used in phase I trials to select appropriate doses and in phase II trials to assess response. Breast density volume and certain serum markers such as insulin-like growth factor-1 are also being studied as potential risk and response biomarkers. Reversal or prevention of advanced IEN as well as modulation of other risk biomarkers in randomized phase II and phase III trials is being evaluated as a means of more efficiently evaluating prevention drugs in the future. A number of agents are being developed that target molecular abnormalities in IEN, have fewer or different side effects than tamoxifen, and may be effective in ER-negative or tamoxifen-resistant disease.
 ...
PMID:Chemoprevention for high-risk women: tamoxifen and beyond. 1190 36

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.
 ...
PMID:[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer]. 1214 1

Nonpregnant/nonlactating women who do not menstruate for at least 6 months have secondary amenorrhea. Stress can induce it. Physical changes can also cause it. Oral contraceptives and other drugs can also bring about secondary amenorrhea. Genital tuberculosis (TB) destroys the endometrium thereby causing secondary amenorrhea. Physicians should initiate antibiotic treatment in women with TB. Further, high levels of prolactin stimulated by an overactive anterior pituitary gland or by a pituitary tumor can produce secondary amenorrhea. Physicians should routinely ask these women if they have hot flashes. These may indicate early climacteric indicated by high levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Prognosis for a return to menstruation is poor if it is indeed responsible. Further, they should also note changes in hair growth. Any such changes may mean an ovarian tumor, polycystic ovaries, or adrenal disease. If adrenal disease is the cause, the level of serum prolactin should be determined. If a high level of prolactin is found, an X-ray should be taken of the pituitary fossa. If it reveals that the clinoid process had eroded or the floor has doubled, a pituitary tumor may exist. If ovarian cancer is responsible, physicians should begin thyroxine treatment. They should prescribe bromocryptine if a pituitary tumor does not exist yet hyperprolactinemia does. Menstruation should return in about 6 weeks. Low or normal levels of FSH and/or LH may indicate that the hypothalamus does secrete gonadotropic releasing factor. Then physicians should administer clomiphene. Menstruation should return in 1-3 months. Women should continue taking clomiphene until they conceive or withdraw from treatment. Physicians should routinely conduct a examination between treatment courses because enlarged ovaries occur in 7% of the treatment cycles. If clomiphene fails, physicians may try gonadotropin treatment. Some surgical procedures may also treat secondary amenorrhea when other treatment fails.
 ...
PMID:Modern management of secondary amenorrhoea. 1228 31

A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate neoplasia. Twenty men, ages 40 and above, with stage B, C, or D adenocarcinoma of the prostate were treated with a multiple-dose regimen of a soy isoflavone formulation (delivering approximately 300 or 600 mg/day genistein and half this much daidzein) for 84 days. The delivered dose of isoflavones was more than 10-fold higher than that typically taken by prostate cancer patients. In men with prostate cancer, relatively minor side effects of chronic isoflavone treatment were observed including some estrogenic effects (breast changes, increased frequency of hot flashes). Serum dehydroepiandrosterone was decreased by 31.7% (P = 0.0004) at the end of treatment. Except for those subjects whose prostate-specific antigen (PSA) values were below 0.4 ng/ml, subjects had a history of increasing PSA levels prior to the trial. This increase continued during the trial both while on soy isoflavones and after treatment was discontinued. On average the rate of rise accelerated after soy isoflavones were discontinued, but that difference did not attain statistical significance. Genistein and daidzein were rapidly cleared from plasma and excreted in urine. Pharmacokinetic data for chronic dose administration were similar to single-dose administration for the isoflavones investigated except that we observed slightly longer circulation time for daidzein.
 ...
PMID:Clinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasia. 1523 50


<< Previous 1 2 3 4 Next >>