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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen (NSC-180973), a synthetic antiestrogen, was studied for efficacy and toxicity in patients with metastatic breast adenocarcinoma. Two dose levels were used, 10 mg bid and 15 mg/m2 bid, in separate groups. In the 10-mg bid dosage group, 30 of the 31 patients were considered evaluable for efficacy. Five complete and 11 partial responses were recorded, for an overall response rate of 53%. In the 15-mg/m2 bid dosage group, 44 of the 45 patients were considered evaluable for efficacy. Three complete and 16 partial responses were recorded, for an overall response rate of 43%. All 76 patients were evaluated for toxicity. Side effects were generally mild, consisting mostly of hot flushes, transient leukopenia, transient thrombocytopenia, nausea, and fluid retention. A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the test as a means to select patients for tamoxifen treatment. The conclusion from this study is that tamoxifen used as a single agent is an effective drug with minimal toxicity for treatment of metastatic breast adenocarcinoma.
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PMID:Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. 79 26

Tamoxifen and trioxifene are antiestrogens that appear to have different endocrine effects when tested in rats. Whereas tamoxifen has considerable clinical activity, trioxifene is a new antiestrogen with undefined clinical activity. Thirty-six patients were treated with graded doses of trioxifene. The low-dose group (0.5 to 12 mg/m2 twice daily) had a 21% response rate in 24 subjects, and the high-dose group (40 to 100 mg/m2 twice daily) had a 33% response rate in 12 patients (P = 0.13). The time to treatment failure was 67 days and 178 days for the low- and high-dose groups, respectively. Toxicities were non-dose dependent; those of moderate frequency included leukopenia (41%) and nausea (31%). Tamoxifen reduced both prolactin and inducible growth hormone (GH). Trioxifene, although reducing prolactin, differed from tamoxifen in that an increase in inducible GH occurred. Furthermore, a striking dose-dependent decrease in luteinizing hormone and lesser decrease in follicle-stimulating hormone occurred only in the trioxifene-treated patients. This implies an intrinsic estrogenic action of trioxifene in man. Trioxifene is no more efficacious than tamoxifen and has more toxicity.
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PMID:A phase I/II investigation of trioxifene mesylate in advanced breast cancer. Clinical and endocrinologic effects. 307 61

Preliminary analysis of adjuvant chemo-endocrine therapy for 193 breast cancer patients was performed. The patients consisted of 38 cases of Stage I, 124 cases of Stage II and 31 cases of Stage III. Therapeutic regimen was randomly divided into three groups; (1) Tamoxifen (TAM), (2) TAM + ftorafur (FT-E) and (3) TAM + FT-E + Adriamycin. Side effects among the three therapeutic groups were comparatively studied. Anorexia and nausea were observed in 1.4%, 17.1% and 60% of the patients, respectively. Leucopenia of less than 3,000 and alopecia were remarkably seen in the patients treated with regimen 3. Liver dysfunction was observed in 10.9% of group 1, 29.5% of group 2 and 13.3% of group 3, respectively. Gastrointestinal symptoms and liver dysfunction were important side effects.
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PMID:[Preliminary report of adjuvant chemo-endocrine therapy for breast cancer]. 391 52

Tamoxifen and its principle metabolite N-desmethyltamoxifen can modulate multi-drug resistance in vitro. Tamoxifen 480 mg/day was given for 6 days with oral etoposide on days 4-6 to 17 patients with advanced solid tumours. Venous thrombosis (2 patients), reversible neurological toxicity (1 patient), and WHO grade III nausea/vomiting (3 patients) related to tamoxifen were observed but overall toxicity was manageable. One partial response occurred in 15 assessable patients. Mean plasma concentrations of tamoxifen and N-desmethyltamoxifen increased to 4.3 mumol/l and 2.7 mumol/l, respectively, by day 6. Plasma concentrations corresponding to active in vitro levels were attained by most patients.
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PMID:High-dose (480 mg/day) tamoxifen with etoposide: a study of a potential multi-drug resistance modulator. 826 8

Previous work has demonstrated the importance of the Protein Kinase C (PKC) signal transduction system in regulating the growth rate of malignant gliomas in vitro. Tamoxifen inhibits PKC in a minority of malignant gliomas within the micromolar concentration range in vitro, a property distinct from its estrogen receptor blockade effect. Tamoxifen was administered orally in very high dosages to 11 patients (9 males:2 females, age range 26-73, mean 45 years) with malignant gliomas (anaplastic astrocytoma or glioblastoma multiforme) who had failed treatment with external beam radiation therapy (and additional chemotherapy in 2). The dosage administered was estimated to be that necessary to achieve tissue concentrations within the low micromolar range, shown necessary to inhibit PKC in these tumors in vitro, and is approximately 5 times that used for standard antiestrogen therapy. Tumor reduction on radiographic images (MRI and PET [18FdG uptake]) with clinical improvement occurred in 3 patients; halting of tumor progression clinically and radiographically occurred in an additional patient. Of the remaining seven patients, three patients had marked and rapid progression of their disease despite treatment (dead after 3, 4, and 6 months respectively). Complications of treatment included a deep venous thrombosis requiring anticoagulation in one patient, nausea in one patient, and "hot-flashes" in a third patient. Tumor biopsy and measurement of tamoxifen and its active metabolite within the tumor of one patient (non-responder) showed levels within the middle of the in vitro therapeutic range. Follow-up of alive patients ranges from 4-18 months (mean 10 months). These encouraging preliminary results in a minority of these patients suggests some potential for this type of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. 838 28

Tamoxifen is a nonsteroidal anti-estrogen frequently used in breast cancer therapy. Side effects to tamoxifen are uncommon (2%) but should be recognized and detected early by careful follow-up. Tamoxifen adjuvant therapy is absolutely indicated in postmenopausal breast cancer with estrogen-receptor--positive nodes. Recently, this indication has been extended to negative-node postmenopausal breast cancer. Mild acute side effects are the most frequent: hot flushes, menstrual irregularity, nausea, headache, vertigo, minimal modifications in blood cell counts. However, more serious accidents can occur. Increased risk of thromboembolism is linked to a fall in the level of antithrombin III. Ocular toxicity can occur. If such ocular lesions are diagnosed early enough, they can be cured by promptly withdrawing treatment. For patients given tamoxifen, there appears to be a small increase in risk of endometrial carcinoma, especially if the daily dose is > 30 mg. This over-risk requires adequate detection based on sufficient knowledge of the usual tamoxifen-related modifications in the endometrium. Physicians should also be aware of two favorable effects. Tamoxifen therapy leads to decreased cardiovascular morbidity and mortality in postmenopausal women and is associated with a significant increase in lumbar bone density. Risk of interaction with oral anticoagulants has been reported. We discuss here practical steps in the follow-up of women treated with tamoxifen.
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PMID:[Surveillance of patients treated with tamoxifen]. 868 11

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrogen receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In addition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine therapy for women with metastatic breast cancer. Tamoxifen, acting predominantly as an estrogen agonist in the liver, has generally favourable effects on serum lipids in postmenopausal women. In addition, tamoxifen has been shown to preserve bone mineral density and may even decrease the risk of osteoporosis in these women. Most patients treated with tamoxifen have minimal adverse effects. Vasomotor symptoms are the most commonly reported events. Less frequently, vaginal discharge or dryness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has been suggested in some adjuvant trials. Rarely, ocular toxicity and hepatotoxicity are found. The adverse effect of primary importance is the increased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage, similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefits of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all women with metastatic breast cancer. Should tamoxifen prove to be an effective chemopreventive agent for breast cancer, the risks and benefits of treatment will have to be more carefully assessed for this setting.
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PMID:Tamoxifen in postmenopausal women a safety perspective. 893 95

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.
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PMID:Phase I and II studies of toremifene. 916 2

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.
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PMID:High-dose toremifene vs tamoxifen in postmenopausal advanced breast cancer. 916 4

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.
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PMID:Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer. 1122 15


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