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

Recent trials comparing single-agent vs combination therapy in metastatic breast cancer suggest that it may be time to reconsider the belief that combination chemotherapy is the gold standard of treatment. Based on the limited randomized trial data available to date, high-dose chemotherapy with stem-cell rescue should not be viewed as "state-of-the art" treatment for metastatic disease and should be used only in the context of clinical trials. Recent trials have explored the optimal dosing and scheduling of the taxanes, as well as the possible role of these agents in combination regimens. Capecitabine (Xeloda), a new oral fluoropyrimidine, appears to be comparable in efficacy to CMF (cyclophosphamide, methotrexate, and fluorouracil), and preclinical data suggest possible synergy between this agent and the taxanes. Other promising agents under study include liposome-encapsulated doxorubicin (TLCD-99), an immunoconjugate linking a chimeric human/mouse monoclonal antibody to doxorubicin molecules; MTA (LY231514), a multitargeted antifolate; and marimistat, a broad-spectrum matrix metalloproteinase inhibitor. Tamoxifen (Nolvadex) remains the most important hormonal agent, but new antiestrogens and selective estrogen receptor modulators (SERMs) may provide alternatives. The potential role of new aromatase inhibitors as first-line hormonal agents requires further study. Finally, the possible synergy between trastuzumab (Herceptin), a recombinant humanized monoclonal antibody to the HER-2/neu protein, and paclitaxel (Taxol) is being studied in two clinical trials.
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PMID:Update on the management of advanced breast cancer. 1035 85

Colorectal cancer remains one of the major causes of cancer death worldwide, but the past few years have witnessed the development of a number of new, effective treatment options, which have led to considerable improvement in the survival rate for patients suffering from this common cancer. The advent of agents such as capecitabine (Xeloda), irinotecan (Camptosar), and oxaliplatin (Eloxatin), and newer molecular targeted agents such as cetuximab (Erbitux) and bevacizumab (Avastin) brought innovation to the treatment of colorectal cancer. Oncologists are no longer restricted to using fluorouracil and its variations as the only active treatment, and the number of patients who are able to live longer continues to increase. Patients presenting with stage III cancer can expect a greater chance for cure, and those presenting with metastatic disease can expect a median survival approaching 2 years.
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PMID:Progress in the development of novel treatments for colorectal cancer. 1521 91

Colorectal cancer is the second most common cause of cancer-related death in the United States. Approximately 30% to 40% of patients with colorectal cancer have locoregionally advanced or metastatic disease on presentation and cannot be cured with surgical therapy. After many years without significant change, systemic therapy for colorectal cancer is rapidly evolving. The past decade has seen the introduction of new chemotherapeutic agents such as irinotecan (Camptosar), oxaliplatin (Eloxatin) and the oral 5-FU prodrug capecitabine (Xeloda). Combination studies of these new agents with the standard 5-FU/leucovorin have extended median survival in patients with advanced colorectal cancer for up to 21 months. In addition, targeted agents with activity in colorectal cancer have emerged and are promising. This article reviews the current treatment recommendations for patients who present with advanced colorectal cancer. Survival in patients with advanced colorectal cancer is on a positive trajectory. The hope that some patients with advanced disease will be long-term survivors (even without surgery) appears to be within the range of possibility.
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PMID:Current strategies in previously untreated advanced colorectal cancer. 1521 92

Patients with metastatic breast cancer (MBC) require chemotherapy that improves outcomes without compromising quality of life. To achieve optimal outcomes with chemotherapy, treatment choices should be influenced by patient and disease characteristics, as well as patient preferences. Capecitabine (Xeloda; F. Hoffmann-La Roche, Basel, Switzerland) combined with docetaxel achieves significantly superior response rates, time to progression, and overall survival compared with single-agent docetaxel. With a manageable safety profile, capecitabine/docetaxel is a particularly appropriate option for younger, fitter patients with rapidly progressing disease and/or visceral metastases. In addition, studies show that dosing flexibility with capecitabine/docetaxel allows management of side effects without compromising efficacy. However, for older patients and those with comorbidities or more indolent disease, single-agent capecitabine may be more appropriate. Studies show that front-line capecitabine is a highly effective and well-tolerated alternative to standard intravenous treatments. The activity of capecitabine in the first-line treatment of MBC is underpinned by its consistently high activity in MBC. As an oral agent that causes minimal alopecia and myelosuppression, capecitabine has the potential to significantly improve patient quality of life and convenience. In summary, the treatment of MBC will always need to be individualized, but a large body of evidence indicates that capecitabine, whether alone or in combination, can be offered to women early in the disease course.
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PMID:Optimizing the management of HER2-negative metastatic breast cancer with capecitabine (Xeloda). 1549 Mar 71

Significant advances have been made in the treatment of advanced colorectal cancer over the past 5 years, namely due to the introduction of three novel cytotoxic agents-capecitabine (Xeloda), irinotecan (Camptosar), and oxaliplatin (Eloxatin)-and the recent approval of two biologic agents-bevacizumab (Avastin) and cetuximab (Erbitux). During this time period, the median survival of patients with advanced, metastatic disease has gone from 10 to 12 months to nearly 24 months. Intense efforts have focused on identifying novel targeted therapies that target specific growth factor receptors, critical signal transduction pathways, and/or key pathways that mediate the process of angiogenesis. Recent clinical trial results suggest that the anti-VEGF antibody bevacizumab can be safely and effectively used in combination with each of the active anticancer agents used in colorectal cancer. Despite the development of active combination regimens, significant improvements in the actual cure rate have not yet been achieved. Combination regimens with activity in advanced disease are being evaluated in the adjuvant and neoadjuvant settings. The goal is to integrate these targeted strategies into standard chemotherapy regimens so as to advance the therapeutic options for the treatment of advanced colorectal cancer. Finally, intense efforts are attempting to identify the critical molecular biomarkers that can be used to predict for either clinical response to chemotherapy and/or targeted therapies and/or the drug-specific side effects. The goal of such studies is to facilitate the evolution of empiric chemotherapy to individually tailored treatments for patients with colorectal cancer.
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PMID:Current therapies for advanced colorectal cancer. 1594 40

A large number of patients with colorectal cancer have relatively early disease, and thus, adjuvant therapy has the potential to save lives. In stage III patients, there has been a steady improvement in 3-year disease-free survival with the use of 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine (Xeloda); Hoffmann-La Roche Inc., Nutley, NJ, http://www.rocheusa.com) regimens. A median survival longer than 20 months was observed in patients with metastatic disease when treated with combination chemotherapy containing oxaliplatin (Eloxatin); Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) or irinotecan (Camptosar); Pfizer Pharmaceuticals, New York, http://www.pfizer.com). This has led to 5-FU/LV/oxaliplatin becoming standard therapy, along with 5-FU/LV/irinotecan. New data confirm the beneficial effect on disease-free survival of adding oxaliplatin to adjuvant colorectal cancer regimens based on 5-FU. These regimens show an effect when given in bolus as well as in infusional schedules. Interest in future adjuvant regimens focuses on the potential additional benefit of molecularly targeted agents, such as bevacizumab (Avastin); Genentech, Inc., South San Francisco, CA, http://www.gene.com), and on the ability of applied genomics to distinguish between high- and low-risk populations.
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PMID:Rapid evolution in colorectal cancer: therapy now and over the next five years. 1627 53

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.
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PMID:Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer. 1704

Capecitabine (Xeloda) is an oral 5-fluorouracil pro-drug used in the treatment of two of the commonest cancers: breast and colorectal. This report concerns a 43-year-old woman with metastatic cancer of the sigmoid colon who developed cardiac chest pain 5 days after starting capecitabine therapy. Capecitabine-induced cardiac symptoms have previously been reported but infrequently. In the main they have documented pain and electrocardiogram (ECG) changes associated with exercise. This case report is of a patient with minimal cardiac risk factors, who had ischaemic cardiac pain with widespread ECG changes at rest that resolved with a nitrate infusion. Coronary vasospasm is proposed as the probable mechanism for the cardiac ischaemia and dramatic ECG changes. Capecitabine is now in widespread use and so physicians will encounter an increasing number of patients using this therapy. In the light of this, it is important that doctors in emergency and acute medicine are aware of its treatable cardiac side effects.
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PMID:Capecitabine-associated coronary vasospasm: a case report. 1843 78

Colorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years. Beside US Food and Drug Administration approval of the cytotoxic agents irinotecan (Camptosar), oxaliplatin (Eloxatin), and capecitabine (Xeloda), the increasing understanding of molecular pathways that comprise the cell cycle, apoptosis, angiogenesis, and invasion has provided novel targets in cancer therapy. The biologic agent bevacizumab (Avastin), an inhibitor against vascular endothelial growth factor, and cetuximab (Erbitux) and panitumumab (Vectibix), monoclonal antibodies to epidermal growth factor receptor, have demonstrated their efficacy in clinical trials. This article reviews the mechanisms of action and possible markers of resistance, and summarizes data on the clinical efficacy of targeting agents.
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PMID:Targeting metastatic colorectal cancer in 2008: a long way from 5-FU. 1847 17

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.
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PMID:The combination of FOLFOX4 and bevacizumab may enable salvage surgery of unresectable liver metastases in colon cancer. 1935 9


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