Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.
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PMID:Aminoglutethimide in patients with metastatic breast cancer. 246 35

In an attempt to increase the clinical activity of 5-fluorouracil (5-FU) by blocking the thymidine salvage pathway, 15 patients with refractory metastatic breast cancer (MBC) were treated with oral dipyridamole (D): 75 mg p.o. q.i.d. and 5-FU: 400 mg/m2 i.v. by bolus for 5 consecutive days, every 28 days. All the patients were pretreated with 5-FU and an anthracycline-based regimen. Toxicity was minimal, with 8 patients experiencing a D-related moderate headache. Although no objective responses were seen, two patients with 5-FU refractory disease showed tumor shrinkage. A different D schedule and the addition of folinic acid (FA) to 5-FU might provide better results and deserves further evaluation.
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PMID:5-Fluorouracil and dipyridamole in metastatic breast cancer: a pilot study. 280 94

Plasma retinol levels and toxicity were evaluated in thirteen metastatic breast cancer patients treated orally with high-dose (300,000 I.U./day) retinyl acetate in combination with oral tamoxifen. Following the first dose of the drug, there was a drop of plasma retinol concentrations followed by a recovery to the pre-treatment levels and by a further increase to reach a plateau six to eight hours after drug administration. During the first two months of treatment cumulative increase of plasma retinol was seen, and long-term systemic concentrations in the +50-60% range level were maintained by the treatment. The toxicity observed was acceptable and included gastrointestinal symptoms, skin toxicity and headache. These toxicities could be related to the long-term increase of retinol systemic concentrations. We concluded that the daily dose of 300,000 I.U. retinyl acetate can be administered to cancer patients over a period of several months, is well tolerated and yields a substantial increase of systemic retinol.
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PMID:Plasma retinol levels and side effects following high-dose retinyl acetate in breast cancer patients. 321 64

Leuprolide (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered to 26 premenopausal women with metastatic breast cancer. Of 25 evaluable patients, 11 (44%) had a partial response with a median duration of 39 weeks and five (20%) remained stable. Six patients showed early rapid progression of their disease. Toxicity was mild and included hot flashes, nausea, vomiting, and headache. Leuprolide induced amenorrhea in all patients who received treatment for ten weeks or longer. We conclude that this GnRH analogue provides a safe and effective means of producing medical castration in premenopausal patients with metastatic breast carcinoma.
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PMID:Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. 392 58

Brain metastases occur clinically in about 10% of patients with stage IV breast cancer, in the setting of widespread extracranial metastases. Prognosis is poor and management is aimed at relieving acute symptoms and improving neurologic status, as well as controlling the metastatic disease. Therapies include surgery, radiotherapy, chemotherapy, and hormonal therapy, used alone or in combination. Performance status is the single most important factor determining treatment choice. In selected patients, surgery can improve survival and performance status. Radiotherapy is the palliative treatment of choice, providing rapid relief of symptoms, especially headache. Recent innovations include accelerated split courses of radiotherapy given in two or three daily fractions, use of radiosensitizers, brachytherapy, and radiosurgery. Systemic therapy remains controversial, but studies show that cytotoxic agents can be palliative against brain metastases if the primary tumor is sensitive to the drug or drugs used.
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PMID:Management of brain metastases from breast carcinoma. 768 Aug 80

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions.
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PMID:Headache, circumoral paresthesia, and facial flushing associated with high-dose carmustine infusion. 913 80

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.
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PMID:Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer. 952 27

In an open, prospective, multicentre phase III clinical trial 73 patients with newly diagnosed, metastatic breast cancer were enrolled. Most of them were hormone-receptor-positive. All patients were pre- or perimenopausal and treated with monthly sc. injections of 3.75 mg leuprorelinacetate-depot as monotherapy until disease progression. 50/73 patients (68.5%) had low-risk metastatic disease. A marked reduction of gonadotropin levels resulted in a profound and sustained suppression of the oestradiol levels to castration range (30 pg/ml) during the entire treatment period. The overall response rate based on the best response during treatment was as follows: CR + PR in 25/73 (34.2%) [25.1-44.4%] and CR + PR + SD in 42/73 patients (58%) [47.2-67.4%] respectively. The median time to progression (TTP) was 6 months and the median overall survival (OS) 24.3 months. Both parameters differed significantly when responder (CR/PR) and non-responder (NC/PD) were compared: 18.6 +/- 2.4 [13.9-23.4] vs. 5.8 +/- 0.6 [4.7-7.0] months (TTP, p < 0.0001) and 41.5 +/- 3.0 [35.5-47.5] vs. 15.6 +/- 2.4 [11.3-20.5] months (OS, p = 0.0019). The median duration of response was 12 (range: 3-48) months. Premenopausal low-risk patients without previous adjuvant treatment after primary surgery showed the best response during the GnRHa treatment. The main side effects (hot flushes, increased sweating, headache etc.) were related to oestradiol suppression. Treatment was well tolerated leading in only one case to a premature withdrawal due to side effects. Leuprorelinacetate-depot is a safe and effective palliative drug for pre- and perimenopausal metastatic breast cancer patients. Like other GnRH-agonists which have been evaluated for this indication, leuprorelinacetate-depot can be used as first-line endocrine treatment in these patients.
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PMID:[Primary endocrine therapy as pre- and perimenopausal metastatic breast carcinoma with leuprorelin acetate depot. German Leuprorelin Study Group]. 965 99

Amplification of the human epidermal growth factor receptor 2 protein (HER2) in primary breast carcinomas has been shown to correlate with poor clinical prognosis for certain patients. Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, California) is a highly purified recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that binds with high affinity and specificity to the extracellular domain of the HER2 receptor. In vitro and in vivo preclinical studies have shown that administration of trastuzumab alone or in combination with paclitaxel or carboplatin significantly inhibits the growth of breast tumor-derived cell lines that overexpress the HER2 gene product. At therapeutic doses in breast cancer patients, the mean half-life of trastuzumab is 5.8 days. Trastuzumab serum concentrations reach steady state with mean trough and peak concentrations of 79 microg/mL and 123 microg/mL, respectively. In a 222-patient, single-arm clinical study, treatment with a loading dose of trastuzumab 4 mg/kg administered IV followed by weekly IV doses of 2 mg/kg produced an overall response rate of 14% (2% complete remission and 12% partial remission). The beneficial effects were greatest in patients with the greatest degree (3+) of HER2 protein overexpression. In another clinical study, 469 women with metastatic breast carcinoma were randomized to a paclitaxel or anthracycline-plus-cyclophosphamide regimen with or without trastuzumab. The overall response rate was significantly greater in the trastuzumab-plus-chemotherapy group than in the chemotherapy-alone cohort. The magnitude of observed effects was greatest with pacli taxel plus trastuzumab. The most common adverse effects attributed to trastuzumab in clinical studies were fever and chills, pain, asthenia, nausea, vomiting, increased cough, diarrhea, headache, dyspnea, infection, rhinitis, and insomnia. Trastuzumab in combination with chemotherapy can lead to cardiotoxicity, leukopenia, anemia, diarrhea, abdominal pain, and infection. Trastuzumab has been approved by the US Food and Drug Administration as a single agent for the treatment of patients who have metastatic breast cancer involving overexpression of the HER2 protein and who have received 1 or more chemotherapy regimens; in combination with paclitaxel, it has been approved for the treatment of such patients who have not received chemotherapy.
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PMID:Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. 1021 34

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.
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PMID:Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. 1116 70


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