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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer. To determine the tolerability and efficacy of increasing doses of megestrol acetate in the treatment of metastatic breast cancer, we conducted a phase I/II study among 57 patients. Three patients each received 480, 800, and 1280 mg/d; 48 patients received 1600 mg/d. Of the 57 patients, 56 patients had had disease progression on prior hormone therapy, chemotherapy, or both. Twenty-seven patients had previously received standard-dose MA (160 mg/d). Among the 37 patients with measurable disease, high-dose megestrol acetate (HDMA) produced 6 (16%) complete responses (CRs) and 6 (16%) partial responses (PRs); 11 patients achieved stable disease (SD). HDMA resulted in improvement or stabilization in 12 of the 20 patients with evaluable, non-measurable disease. There were no responses among the 6 patients with liver metastases. Among the 27 patients who were previously treated with standard-dose MA, including 9 patients with primary treatment failure, HDMA resulted in 1 CR, 3 PRs, and 10 SD. Toxicities, which were mild and reversible, included fluid retention, hypertension, hyperglycemia, and mild congestive heart failure. Two patients had superficial phlebitis. The most profound side effect was weight gain which occurred in 43 patients (75%). This study suggests a dose-response relationship for MA in the treatment of advanced breast cancer. A randomized trial to determine the optimal dose is ongoing.
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PMID:A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer. 175 60

This study was performed to determine the toxicity and effectiveness of megestrol acetate used with aminoglutethimide-hydrocortisone in the treatment of patients with metastatic breast cancer. Forty-five patients were treated, 29 of whom were fully eligible. Twelve of the 45 who had diabetes and/or hypertension were also analyzed. All had measurable sites of disease. The median age was 63 years, and the median time from first recurrence to on-study was 19 months. Approximately half the patients already had chemotherapy, and about 90% had hormone therapy for advanced disease. The most common side effects were skin rash, weight gain, hyperglycemia, and renal and neurologic problems. No life-threatening or lethal toxicities were reported. The overall response rate (complete or partial) among the fully eligible patients was 34% (90% confidence intervals from 20% to 51%), with a 5-month median duration of response. Patients with soft tissue, visceral, and osseous disease responded. Seventy-two percent of fully eligible patients have progressed or relapsed. The median time to failure of treatment was 6 months, and the median survival time was 15 months.
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PMID:Combination hormone therapy for metastatic breast cancer. An ECOG study of megestrol and aminoglutethimide. 344 Feb 24

LU 103793 is a synthetic analogue of Dolastatin 15 that inhibits tubulin polymerisation. The aim of this study was to evaluate the efficacy and tolerability of LU 103793 in patients with metastatic breast cancer who had been previously treated with two lines of chemotherapy for advanced disease. Patients received LU 103793 at a dose of 2.5 mg/m(2)/day over 5 min for 5 consecutive days every 3 weeks. Thirty-four patients were enrolled and 23 patients were eligible for the evaluation of efficacy. Eleven patients experienced grade 4 neutropenia. Other related grade 3/4 adverse events included asthenia (three patients), stomatitis (1), myalgia (1) and increase of serum bilirubin (2). The main toxicity was hypertension occurring in seven out of 34 patients. There were no objective responses, 7 patients had stable disease. These results do not support the further evaluation of LU 103793 in metastatic breast cancer patients using this dose and schedule.
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PMID:Phase II study of LU 103793 (dolastatin analogue) in patients with metastatic breast cancer. 1256 83

Vascular endothelial growth factor promotes angiogenesis, an important mediator of growth and metastasis in human breast cancer. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, is under investigation as an anti-angiogenic agent. This phase I/II trial evaluated the safety and efficacy of bevacizumab in patients with previously treated metastatic breast cancer. Seventy-five patients were treated with escalating doses of bevacizumab ranging from 3 mg/kg to 20 mg/kg administered intravenously every other week. Tumor response was assessed before the sixth (70 days) and 12th (154 days) doses. Safety was evaluated during every cycle. Eighteen patients were treated at 3 mg/kg, 41 at 10 mg/kg, and 16 at 20 mg/kg. Four patients discontinued study treatment because of an adverse event. Hypertension was reported as an adverse event in 17 patients (22%). The overall response rate was 9.3% (confirmed response rate, 6.7%). The median duration of confirmed response was 5.5 months (range, 2.3 to 13.7 months). At the final tumor assessment on day 154, 12 of 75 patients (16%) had stable disease or an ongoing response. The optimal dose of bevacizumab in this trial was 10 mg/kg every other week and toxicity was acceptable. These data support the initiation of trials in metastatic breast cancer combining bevacizumab with chemotherapy.
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PMID:A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. 1461 32

Vascular endothelial growth factor (VEGF) has emerged as a key target for the treatment of cancer. As the ligand to the VEGF receptor, it plays a central role in promoting tumor angiogenesis. Overexpression of VEGF leads to poor outcomes in patients with breast cancer and other tumors. Preclinical studies have shown that the humanized monoclonal antibody to VEGF, bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), can reduce tumor angiogenesis and inhibit the growth of solid tumors, either alone or in combination with chemotherapy. As a single agent or added to vinorelbine, bevacizumab has produced encouraging results in phase II clinical trials in patients with refractory metastatic breast cancer. When added to capecitabine chemotherapy in a phase III trial, bevacizumab produced a greater response rate, but did not prolong progression-free survival. This may reflect the late disease stage and poor prognostic factors in the patient population. A large, ongoing, phase III, cooperative group trial is evaluating the effect of bevacizumab in combination with paclitaxel as first-line therapy for metastatic disease. The adverse effect profile of bevacizumab differs from that of cytotoxic chemotherapy and includes hypertension, proteinuria, thrombosis, and epistaxis.
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PMID:Bevacizumab in the treatment of breast cancer: rationale and current data. 1517 15

Cardiac toxicity of chemotherapeutic agents is a rapidly evolving area of increasing significance because of the increasing pool of long-term cancer survivors. The spectrum of cardiotoxicity with chemotherapeutic agents includes hypertension, QTc prolongation, acute cardiomyopathy, and bradyarrhythmias. The most common issue to arise has been cardiomyopathy with anthracyclines. Preventative strategies that have met with some success have included the use of less cardiotoxic analogs such as epirubicin and liposomal anthracycline preparations. The cardioprotectant agent dexrazoxane reduces cardiomyopathy but there are significant toxicity issues. Therefore, the main strategy for preventing cardiotoxicity remains careful monitoring with radionuclide angiography or echocardiography. The role of investigational markers of myocardial injury, such as troponin T or brain natriuretic peptide, remains of great interest. Management is according to conventional management of congestive heart failure. Trastuzumab is an antibody therapy directed against the human epidermal growth factor receptor-2 (HER2) receptor, which increases survival in patients with metastatic breast cancer and is under evaluation in the adjuvant setting. It also causes a decrease in left ventricular ejection fraction (LVEF) in a minority of patients. Incidence is increased if trastuzumab is given in conjunction with paclitaxel or anthracyclines. It differs from anthracycline cardiotoxicity in that it is not cumulative dose-dependent and often improves after withdrawal of treatment. Re-treatment with trastuzumab is often possible. Novel agents under development offer a different spectrum of toxicity to existing anticancer drugs and it appears likely that cardiovascular toxicity will be an important issue for many of these drugs, particularly those that target the tumor vasculature.
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PMID:The prevention and management of cardiovascular complications of chemotherapy in patients with cancer. 1598 6

Anthracyclines and taxanes are among the most active substances used in the treatment of metastatic breast cancer (MBC). Their frequent use in the adjuvant setting and in cumulative toxicities including cardiotoxicity, however, often limit their use in MBC. The trend towards the use of adjuvant trastuzumab-containing regimens, which can also produce cardiotoxicity, adds further support to the need for effective agents with improved tolerability in the metastatic setting. Pegylated liposomal doxorubicin (PLD) can be an effective alternative to conventional anthracyclines for certain women with MBC. In phase III clinical trials, PLD was as effective as doxorubicin and produced significantly less cardiotoxicity in women with MBC. The incidences of myelotoxicity, nausea/vomiting, and alopecia were also lower with PLD, whereas hand-foot syndrome and stomatitis occurred more frequently. Phase II and III trials conducted in women with MBC support the use of PLD monotherapy in patients relapsing after adjuvant anthracycline-containing therapy, in heavily pretreated patients with taxane-refractory disease, in patients with cardiovascular risk factors (e.g. hypertension and mediastinal irradiation), in elderly patients, and in patients for whom specific acute doxorubicin toxicities, such as alopecia, are particularly worrying.
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PMID:Single-agent treatment with pegylated liposomal doxorubicin for metastatic breast cancer. 1804 24

A 53-year-old woman presented to the operating room for surgical correction of pericardial and pleural effusions. Her history included stage IV breast cancer, well-controlled hypertension, and diverticulitis. Although her baseline blood pressure, heart rate, and respirations were normal, she was short of breath with diminished breath sounds on the left side of the lungs and required oxygen, 2 L/min via nasal cannula. The nurse anesthesia student, under the direction of the Certified Registered Nurse Anesthetist (CRNA) and anesthesiologist, induced general anesthesia with etomidate, fentanyl, lidocaine, and succinylcholine. During placement of a double-lumen endotracheal tube, the patient became asystolic. The nurse anesthesia student immediately withdrew the laryngoscope, and the patient returned to normal sinus rhythm. A second attempt at laryngoscopy produced asystole as well. Again, the laryngoscope was withdrawn, and the patient returned to normal sinus rhythm. After resuming ventilation with 100% oxygen and administering atropine, 0.4 mg, the next intubation was successful, producing no untoward effects. Reintubation at the end of the case with a single lumen endotracheal tube was uneventful. The patient was transported to the intensive care unit and mechanically ventilated overnight. The next morning, she was extubated with no further anesthetic complications.
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PMID:Asystole during laryngoscopy of a patient with pleural and pericardial effusions: a case report. 1856 17

The monoclonal antibody bevacizumab, targeted against the angiogenesis factor VEGF has clinical activity against several common cancers. In metastatic breast cancer it improves response rate and time to progression in combination with paclitaxel/docetaxel compared with paclitaxel/docetaxel alone; the drug is currently being investigated in other combination regimens and as adjuvant and neoadjuvant therapy in early breast cancer. It is generally well tolerated. Side effects, including hypertension, proteinuria, thrombosis and bleeding, are uncommon and usually managed easily. Based on the clinical efficacy of bevacizumab, other small-molecule oral antiangiogenesis agents are now also under development.
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PMID:Bevacizumab in the treatment of breast cancer. 1892 48

The growth of new blood vessels, angiogenesis is important for tumour progression and metastasis. Vascular endothelial growth factor (VEGF) plays multiple roles in cancer development. Due to it the VEGF seems to be an optimal therapeutic target in breast cancer therapy. The plasma level of this growth factor is highest early in disease suggests that anti-VEGF agents may provide their greatest benefit in firts-line chemotherapy with metastatic breast cancer (MBC). A phase III trial, E2100 evaluated weekly paclitaxel with or without bevacizumab (Avastin), the specific humanised anti-VEGF monoclonal antibody in patients with previously untreated locally recurrent or MBC, doubling of progression-free survival for all patient subgroups. Bevacizumab is generally well tolerated. The most common adverse events observed in trials hypertension, proteinuria, and wound-healing complications, most of which are grade 1-2 in severity. The registration of bevacizumab for MBC therapy brings new hope for patients. Novel approach of bevacizumab for MBC would be combination chemotherapy and different targeted therapies. Phase III clinical trials of bevacizumab are ongoing in different stages in different settings.
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PMID:[Anti-VEGF therapy with bevacizumab in breast cancer]. 1922 9


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