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

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab) (Genetech, Inc. 2008). This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG) and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical) atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.
 ...
PMID:Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer. 1933 43

Colorectal cancer treatment has experienced important advances in the last 5 years. New targeted therapies have been included in the classical regimens based on 5-fluorouracil, oxaliplatin, or irinotecan. This new approach has brought great revolution in the treatment of this type of cancer. Bevacizumab (Avastin), a new antivascular endothelial growth factor drug, has been shown to improve overall survival in combination with chemotherapy in first-line and second-line settings as compared with standard chemotherapy regimens alone. This case report demonstrates our experience with bevacizumab in a colon cancer patient with liver, lung, and regional lymph node metastases who had a relapse in the liver after adjuvant treatment with capecitabine (Xeloda). The addition of bevacizumab to the FOLFOX4 regimen resulted in a partial response that provided an opportunity for salvage hepatic surgery.
 ...
PMID:The combination of FOLFOX4 and bevacizumab may enable salvage surgery of unresectable liver metastases in colon cancer. 1935 9

The hallmark radiological finding in metastatic brain disease is multiple enhancing lesions. We report a case of metastatic lung cancer to the brain with a lack of contrast enhancement. We believe that this unusual finding is due to inadvertent "treatment" of the metastases with the antiangiogenic agent bevacizumab (Avastin).
 ...
PMID:Nonenhancing brain metastases. 1949 Apr 1

Contrast-enhanced multislice computer tomography (MSCT) has established itself as the standard tomographic imaging method both for diagnosis and for treatment monitoring of hepatic lesions. To clarify local conditions before partial liver resection, diffusion-weighted magnetic resonance tomography (DWI-MRT) can also provide important additional information. In order to meet the criteria for a R0 resection, a margin of 0.5 mm seems to be sufficient. Neoadjuvant chemotherapy aiming to reduce tumour size can be given in parallel with portal artery embolisation without adversely affecting perioperative morbidity and mortality. As far as the management of primary resectable liver metastases is concerned, there is an urgent need for more studies. Despite the relatively limited evidence, adjuvant chemotherapy is currently more widely favoured in Germany than perioperative chemotherapy. There is also considerable need for studies concerning preoperative therapy in patients with liver metastases that are not (yet) resectable. In KRAS wild-type tumours, high response rates (in terms of a reduction in the size of metastases) are achieved with a cetuximab/chemotherapy combination. Bevacizumab/chemotherapy combinations lead to high rates of pathohistological complete and partial remissions. What the best parameter for judging the success of preoperative therapy is remains unknown, and so comparison studies using survival as a 'hard' endpoint must be carried out.
 ...
PMID:[Diagnosis and treatment of liver metastases from primary colorectal tumour]. 1954 96

Renal cell carcinoma (RCC) is very resistant to both chemotherapy and radiotherapy. Localized disease can be cured by surgery but most patients are diagnosed when distant metastases are already present and about 30% of patients relapse after nephrectomy. Until 2 years ago, cytokine-based immunotherapy (interleukin-2 and interferon-alpha) was the only therapeutic option for advanced RCC patients. Fewer than 20% of patients benefit from this treatment, but some of these may experience very prolonged complete responses and progression-free intervals, suggesting a possibility of cure in a very few cases. Thanks to our expanding knowledge of the biology and pathogenesis of RCC, the treatment of this disease has recently undergone a major advance, through the development of potent angiogenesis inhibitors and targeted agents. Bevacizumab, an antibody directed against vascular endothelial growth factor (VEGF), has shown significant activity in combination with interferon-alpha (IFN-alpha). Sunitinib and sorafenib, multikinase inhibitors with proven antiangiogenic activity, have also been approved for the treatment of this tumor. Finally, temsirolimus and everolimus, which belong to the family of mammalian target of rapamycin (mTOR), have shown some activity in selected patients. The aim of this paper is to review clinical trials with these new agents, describing their activity and profiles of toxicity, and to evaluate potential future developmental strategies.
 ...
PMID:A survey of therapy for advanced renal cell carcinoma. 1957

black triangle Bevacizumab is a recombinant, humanized vascular endothelial growth factor (VEGF) monoclonal antibody that inhibits tumor growth and tumor metastases. VEGF stimulates angiogenesis in tumors, is involved in early metastatic processes, and is overexpressed in non-small cell lung cancer (NSCLC). black triangle The addition of bevacizumab to standard chemotherapy significantly delayed disease progression in two large, randomized, phase III trials in chemotherapy-naive patients with advanced, nonsquamous NSCLC. In the open-label E4599 trial, median overall survival duration was significantly extended by 2 months and median progression-free survival was significantly increased by 1.7 months when intravenous bevacizumab 15 mg/kg once every 3 weeks was added to first-line carboplatin/paclitaxel therapy compared with carboplatin/paclitaxel alone. black triangle In the double-blind AVAiL trial, median progression-free survival was significantly increased (by 0.6 and 0.4 months) by the addition of intravenous bevacizumab 7.5 or 15 mg/kg once every 3 weeks to first-line cisplatin/gemcitabine therapy compared with placebo plus cisplatin/gemcitabine. However, median overall survival duration was not significantly improved (13.6 and 13.4 months vs 13.1 months). black triangle Response rates in the E4599 and AVAiL trials were 30-35% in patients receiving bevacizumab plus platinum-based chemotherapy compared with 15% and 20% without bevacizumab. black triangle The safety and tolerability profile of bevacizumab-containing treatment regimens in patients with advanced NSCLC was generally manageable in the E4599 and AVAiL trials, and in two large, ongoing, trials (the open-label SAiL and the observational ARIES studies).
 ...
PMID:Bevacizumab plus platinum-based chemotherapy: in advanced non-small cell lung cancer. 1962 70

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), and it has shown promise as a clinical agent against metastatic colorectal cancer, and particularly in combination with chemotherapy. Bowel perforation is a known risk that's associated with bevacizumab use, but the etiology is unknown. Here we report on two cases of metastatic colorectal cancer in which the patients suffered from intestinal perforation after chemotherapy with bevacizumab. For the first case, a 47 year-old man had rectal cancer with concurrent liver and lung metastasis. He underwent chemotherapy with 5-fluorouracil, irinotecan and bevacizumab. Fever and abdominal pain developed seven days later, and rectal perforation was identified upon exploration 13 days later. For the second case, a 48 year-old woman had sigmoid colon cancer with peritoneal and ovary metastases. After seven days of chemotherapy with 5-fluorouracil, oxaliplatin and bevacizumab, exploratory surgery revealed a perforation at the ileum.
 ...
PMID:Intestinal perforation in colorectal cancers treated with bevacizumab (Avastin). 1968 63

In metastatic colorectal cancers (CRC), progress of chemotherapies in 40 years greatly increased their median survival from 6 to 8 months to 20 months. The first step of this development has been: the discovery of 5-fluorouracil, its optimisation by folinic acid and continuous perfusions. In the years 1990 to 2000, oxaliplatin and irinotecan opened the era of polychemotherapies. Their use in fisrt line treatment is not mandatory for all patients for whom chemotherapy may only have a palliative role without need for high response rates as for patients with symptomatic metastases or metastases hardly resectable. Targeted therapies have increased the life expectancy of the metastatic CRC and for some of them to facilitate secondary resections. Bevacizumab, an anti-VEGF antibody, in combination with an irinotecan based regimen increased dramatically the life expectancy with an acceptable toxicity, at least in patients of less than 70 years old. Efficacy of bevacizumab has also been demonstrated in combination with oxaliplatin based regimen (XELOX and FOLFOX) in first and second line, and in combination with 5-fluorouracil alone. Presently, bevacizumab is the most used targeted therapies in first line chemotherapy in combination with FOLFIRI, FOLFOX or XELOX. Cetuximab and panitumumab have first demonstrated their efficacy in the population of fully resistant patients to chemotherapies with a progression free survival gain of about 4 months as single treatment (cetuximab and panitumumab) or combined to irinotecan (cetuximab). Two studies have demonstrated that the adjonction of cetuximab in the first line treatment to FOLFIRI or FOLFOX increased the response rates. The presence of epithelial growth factor receptors (EGFR) at the cell'surface in immunohistochemistry is not a prerequisite for responses to cetuximab and panitumumab, and only patients with tumors without mutation of oncogene KRAS (60% of patients) are able to respond to anti-EGFR. This activity for the KRAS non mutated population has also been demonstrated in patients resistant to chemotherapy, compared to best supportive cases with panitumumab and with cetuximab. Thus, utilisation of anti-EGFR is only authorized in non mutated KRAS tumors and for the first time in metastatic CRC, we have the possibility to enrich the population in selecting non mutated KRAS population and to treat only patients having increased chance of response and of secondary resections of initially non resectable metastases. The cost of these targeted therapies is elevated and we need to find factors which will allow a personalized medicine with the dual selection of the good drug for the right patients.
 ...
PMID:[Targeted biotherapy: a revolution in the management of patients with colorectal cancer?]. 1971 58

One of the most significant developments in medical oncology practice has been the approval of various antiangiogenic drugs for the treatment of a number of different malignancies. These drugs include bevacizumab (Avastin), the anti-VEGF monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in patients who have advanced metastatic disease only or primarily when it is combined with conventional chemotherapy. The reasons for the chemo-enhancing effects of bevacizumab are unknown, and this is a subject that we have been actively studying along with additional ways that antiangiogenic drugs may be combined with chemotherapy. In this respect, we have focused much of our effort on metronomic low dose chemotherapy. We have been studying the hypothesis that some chemotherapy drugs at maximum tolerated doses or other cytotoxic- like drugs such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization of proangiogenic cells from the bone marrow which home to and colonize the treated tumors, thus accelerating their recovery. These cells include endothelial progenitor cells. This systemic process can be largely blocked by a targeted antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic chemotherapy, i.e., close regular administration of chemotherapy drugs at low non-toxic doses with no breaks, over prolonged periods of time not only prevents the acute CEP bone marrow response, but can even target the cells. This potential antiangiogenic effect of metronomic chemotherapy can also be boosted by combination with a targeted antiangiogenic agent. Treatment combinations of metronomic chemotherapy and an antiangiogenic drug have moved into phase II clinical trial testing with particularly encouraging results thus far reported in metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable based on long term adjuvant therapy studies in patients. Recent preclinical results using metronomic cyclophosphamide and metronomic UFT in models of advanced metastatic breast cancer suggest that this type of combination might be particularly promising for metronomic chemotherapy in this indication, particularly when combined with a targeted antiangiogenic drug.
 ...
PMID:Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs. 1974 37

Elderly women constitute a large group of breast cancer patients, and after multidimensional geriatric assessment (MGA) only a minor part of them are found in perfect health (=fit), while the remaining display one or more physical or functional limitations or familial/social problems and are therefore categorized as vulnerable or frail (=unfit). Although randomized trials have not produced modest evidence that surgery impacts on ultimate survival of elderly women with hormone-responsive tumors, there is a general consensus that age alone should not prevent surgical local treatment even in unfit women due to the limited morbidity of breast surgery and to the risk of local progression. Activity and safety of AIs appear comparable in elderly women compared to younger counterparts, although concomitant cardiovascular comorbidity and osteoporosis should be closely monitored. Of note, compliance to oral therapy in unfit women and possible interferences with concomitant medications are still poorly documented issues. With the exception of high-risk node positive and estrogen-receptor negative patients, administration of adjuvant chemotherapy for estrogen-receptor positive unfit patients is rarely recommended since the uncertain gain in relapse-free survival is exceeded by the increased risk of toxicity and competitive causes of death. Endocrine-responsive metastatic disease is managed with one or more lines of endocrine treatment as in younger patients. Single agent sequential chemotherapy regimens are to be preferred to combination regimens, which are usually more toxic with a limited survival gain even in younger patients. When and how dose reductions should be applied to unfit patients is highly controversial. Trastuzumab in association with chemotherapy can be administered to elderly patients presenting HER2 overexpressing tumors, although the risk of cardiac adverse events in unfit patients is largely unknown. Bevacizumab-based combinations increase the activity and also toxicity of taxane chemotherapy, and are not a preferred option.
 ...
PMID:Management of primary and advanced breast cancer in older unfit patients (medical treatment). 1976 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>