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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant therapy with chemotherapy and/or radiation therapy in addition to surgery improves outcome for patients with high-risk carcinomas of the colon or rectum. For colon cancer, fluorouracil (5-FU) combined with leucovorin is a current standard of care that improves long-term survival. A recent European trial (MOSAIC) has documented significant improvement in 3-year disease-free survival when oxaliplatin (Eloxatin) was added to infusional 5-FU and leucovorin in the FOLFOX regimen. Two US cooperative group trials will evaluate the addition of antiangiogenesis therapy with bevacizumab (Avastin) to chemotherapy. A third trial will evaluate FOLFOX, irinotecan (Camptosar) combined with infusional 5-FU and leucovorin (FOLFIRI), and the sequential use of FOLFOX followed by FOLFIRI. In rectal cancer, postoperative 5-FU-based chemotherapy combined with irradiation can improve both local tumor control and survival. The German Rectal Cancer Group has recently reported that preoperative combined-modality therapy is less toxic and more effective in preventing local tumor relapse compared to similar treatment given postoperatively. A coordinated pair of cooperative group clinical trials will evaluate oral capecitabine (Xeloda) as a radiation enhancer in the preoperative setting, and the FOLFOX and FOLFIRI regimens compared to 5-FU and leucovorin following surgery. Predictive and prognostic molecular markers will be studied in these new adjuvant therapy clinical trials for both colon and rectal cancer with the goal of developing future regimens tailored to individual patients. There has been a recent and dramatic increase in the pace of drug development for colorectal cancer which holds promise to further improve curative therapy as part of a multidisciplinary approach in the surgical adjuvant setting.
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PMID:Current status of adjuvant therapy for colorectal cancer. 1521 94

Two of the most promising new targets in the treatment of colorectal cancer are the epithelial growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). Agents that inhibit the EGFR or bind to VEGF have demonstrated clinical activity as single agents and in combination with chemotherapy in phase II and phase III clinical trials. The most promising of these agents are cetuximab, which blocks the binding of EGF and transforming growth factor alpha (TGF-alpha) to EGFR, and bevacizumab, which binds free VEGF. Cetuximab and irinotecan have been evaluated in two clinical studies in the USA (IMCL CP02-0141 and IMCL CP02-9923). Study IMCL CP02-0141 evaluated the antitumor activity of single-agent cetuximab in patients with irinotecan-refractory, EGFR-positive metastatic colorectal carcinoma. There were 6 partial responses in 57 treated patients, for a response rate of 10.5%. Study IMCL CP02-9923 evaluated the combination of cetuximab and irinotecan in a total of 139 patients enrolled at 27 study sites. In this trial 22.5% of patients with progressive disease on irinotecan achieved an objective response (19% by investigator assessment) showing that the combination of cetuximab and irinotecan has antitumor activity in this population. A large randomized phase II trial evaluating similar study populations in Europe confirmed these findings, demonstrating response rates for cetuximab/irinotecan and cetuximab alone of 22.9% and 10.8%, respectively. The other promising agent bevacizumab is a humanized variant of the anti-VEGF monoclonal antibody. VEGF is produced by healthy and neoplastic cells. Its activities are mediated by two receptor tyrosine kinases. VEGF signaling is often a rate-limiting step in physiologic and pathologic angiogenesis. Bevacizumab has been studied as an antiangiogenic cancer therapeutic as a single agent and in combination with chemotherapy in patients with stage III and IV colon cancer. In addition to its direct antiangiogenic effects, bevacizumab may allow more efficient delivery of chemotherapy by altering tumor vasculature and decreasing the elevated interstitial pressure common in tumors. In this regard, some of the most robust phase II data using bevacizumab are from a randomized study of chemotherapy [fluorouracil (5-FU) and leucovorin (LV)] with or without bevacizumab in metastatic colorectal cancer. In this study, treatment with bevacizumab plus 5-FU/LV resulted in higher response rates, longer median time to disease progression, and longer median survival. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to investigate the addition of bevacizumab to first-line irinotecan, 5-FU, and LV chemotherapy (IFL). The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. It was the first large, randomized, phase III survival trial to assess the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Integration of novel agents targeting VEGF and EGFR with irinotecan-based chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. The goal in the future will be to predict which specific chemotherapy and targeted agent combination will most likely benefit individual patients.
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PMID:Integration of novel agents in the treatment of colorectal cancer. 1530 12

When the FDA commissioner announced in February 2004 the approval of Avastin for the treatment of patients with colon cancer, he called angiogenesis inhibitors a fourth modality of anti-cancer therapy. Because angiogenesis inhibitors are relatively less toxic than conventional chemotherapy and have a lower risk of drug resistance, they may also represent a new class of anti-cancer agents, some of which have sufficiently reduced toxicity that they may be safely used long term. These include immunotherapy, vaccines, telomerase inhibitors, apoptosis inducers, low dose metronomic chemotherapy, novel hormonal therapies, gene therapy and others. However, at least 16 endogenous angiogenesis inhibitors have been discovered in the circulation, and/or in the extracellular matrix. These may become the safest and least toxic of anti-cancer therapies. Four are already being administered by injection in clinical trials for cancer. Recently, it has been reported that at least two endogenous angiogenesis inhibitors can be significantly increased in humans (endostatin), and in mice (thrombospondin), by oral administration of small molecules which themselves are already FDA approved for other uses. This finding suggests several new clinical applications for the future, including the possibility of guiding the use of angiogenesis inhibitors by blood or urinary biomarkers, currently being developed, that may detect the presence of cancer before it is symptomatic, or before it can be located by conventional methods.
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PMID:Endogenous angiogenesis inhibitors. 1556 12

Within the revolution of molecular biology in cancer, it should be pointed out the role of monoclonal antibodies clinically utilized as if they were "magic bullets". From the works of Kohler and Milstein in 1975 the evolution has been fast and its inclusion in daily clinical practice gradual. Among the more significant there is anti-CD20 that has revolutionized the treatment of lymphomas. Currently, antibodies conjugated with isotopes derived from anti-CD20 have been produced. Trastuzumab antibody against HER2/neu has opened new prospects in the treatment of breast cancer. Cetuximab antibody against EGFR has achieved good results in the treatment of chemotherapy-resistent colon cancer. Bevacizumab is perhaps the most promising antibody against solid tumors, having shown effectiveness as first line therapy in metastatic colon cancer in combination with chemotherapy.
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PMID:[Antibodies against cancer]. 1571 74

Recently, major developments in the treatment of colon cancer have emerged. These developments include improvements in surgical technique and staging and the introduction of new molecularly targeted pharmacologic agents. Improvements in surgical management involve enhanced staging techniques, allowing more accurate determination of risk of recurrence. Newer agents, such as oxaliplatin, cetuximab, and bevacizumab, now are approved for the treatment of colon cancer. The data associated with use of oxaliplatin in adjuvant and metastatic settings continue to mature; survival benefits are expected to become more fully apparent in the next two years. Bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, when combined with irinotecan, 5-fluorouracil, and leucovorin (IFL), was superior to IFL alone in achieving median and progression-free survival. Cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, when given in combination with irinotecan, achieved an increased objective response and increased time to progression, compared with cetuximab alone, in patients refractory to irinotecan-containing regimens. In addition to surgical and pharmacologic developments, the recognition that genetics and molecular markers play an important role in carcinogenesis has heightened research to integrate this knowledge into practice. Nurses play a pivotal role in the care of patients with colon cancer and must be conversant in the new advances in treatment.
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PMID:Therapeutic options in the management of colon cancer: 2005 update. 1575 97

In early February 2006, Genentech Inc. issued a joint press release with Roche Holding Corporation explaining that their phase III early-stage colon cancer trial of Avastin (bevacizumab, Genentech Inc., South San Francisco, CA) would be stopped after the deaths of four patients. This announcement was the result of preliminary review of the data by the Data Safety Monitoring Board (DSMB) that was formed to monitor the study. What is the DSMB? What criteria does it use to determine whether a study should be stopped early? The purpose of this article is to (a) explain the role of the DSMB, (b) give an overview of the Avastin Adjuvant (AVANT) study, and (c) provide information and resources about clinical trials for practicing RNs in oncology.
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PMID:The role of the data safety monitoring board: why was the Avastin phase III clinical trial stopped? 1670 97

Among patients with colorectal cancer (CRC) diagnosed in the United States, 37.2% are diagnosed with stage III and 27.9% with stage II disease. In locoregionally advanced CRC, surgery is the primary treatment modality and has a curative intent. The survival depends on the pathologic stage and varies from 30%-60% for stage III to 60%-80% for stage II. However, as much as 40%-50% of patients will relapse and require additional treatment of the disease. Clinical failure after resection of CRC is predominantly secondary to the clinical progression of previously undetected distant metastatic disease. Until very recently, the absolute benefit for survival obtained with adjuvant therapy compared with control was about 6%. Introduction of oxaliplatin in the adjuvant setting has shown a reduction of 23% in the risk of relapse when compared with 5-fluorouracil alone (MOSAIC). Recent phase III studies have shown that targeted agents improved survival in patients with advanced-stage CRC. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is the first antiangiogenic drug to show improved efficacy when used in combination with irinotecan and oxaliplatin for first- and second-line treatment of CRC. Cetuximab, another monoclonal antibody targeting epidermal growth factor receptor, has shown efficacy in third-line therapy and promising results in first-line phase II studies. There is great interest in whether the biologic agents bevacizumab and cetuximab can improve survival in the adjuvant-therapy setting. This article reviews the adjuvant therapy for colon cancer and discusses the potential role and current trials involving the targeted agents.
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PMID:Targeted agents for adjuvant therapy of colon cancer. 1679 91

Adjuvant therapy for colorectal cancer consists primarily of combinations of 5-fluorouracil/leucovorin (5-FU/LV) (with infusional or bolus 5-FU) with oxaliplatin or oral capecitabine. The angiogenesis inhibitor bevacizumab and the epidermal growth factor receptor inhibitor cetuximab have shown activity when combined with 5-FU/LV-based regimens as first-line treatment of advanced disease and are currently being evaluated as part of adjuvant therapy in colon cancer. Bevacizumab is being evaluated in combination with FOLFOX4 (5-FU/LV/oxaliplatin), FOLFOX6, or XELOX (capecitabine/oxaliplatin) in the National Surgical Adjuvant Breast and Bowel Project C08 trial, the AVANT (AVastin adjuvANT) trial, and the Intergroup Rectal Adjuvant trial. Cetuximab is being evaluated in combination with FOLFOX4 and FOLFOX6 in the North Central Cancer Treatment Group (NCCTG) N0147 trial and the Pan European Trials in Adjuvant Colon Cancer (PETTAC) 8 trial.
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PMID:Targeted agents for adjuvant therapy of colon cancer. 1717 86

On June 20, 2006, the U.S. Food and Drug Administration (FDA) approved bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin) for the second-line treatment of metastatic carcinoma of the colon or rectum. Efficacy and safety were demonstrated in one Eastern Cooperative Oncology Group (ECOG) open-label, multicenter, randomized, three-arm, active-controlled trial enrolling 829 adult patients. Patients had received a fluoropyrimidine- and irinotecan-based regimen as initial therapy for metastatic disease; or they had received prior adjuvant irinotecan-based chemotherapy and had recurred within 6 months of completing therapy. Treatments included bevacizumab, 10 mg/kg, as a 90-minute i.v. infusion on day 1, every 2 weeks, either alone or in combination with FOLFOX4, or FOLFOX4 alone. The bevacizumab monotherapy arm was closed to accrual after an interim efficacy analysis suggested a possibly shorter survival in that arm. Overall survival (OS), the primary study endpoint, was significantly longer for patients receiving bevacizumab in combination with FOLFOX4 than for those receiving FOLFOX4 alone. The objective response rate was significantly higher in the FOLFOX4 plus bevacizumab arm than in the FOLFOX4 alone arm. The duration of response was approximately 6 months for both treatment arms. Patients treated with the bevacizumab combination were also reported, based on investigator assessment, to have significantly longer progression-free survival. There were no new bevacizumab safety signals. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound-healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, and congestive heart failure.
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PMID:FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. 1740 1

Bevacizumab, a recombinant humanised monoclonal antibody against vascular endothelial growth factor, is approved in Europe as first-line therapy for metastatic breast cancer (mBC) and metastatic carcinoma of the colon or rectum (mCRC); the European Medicines Agency gave a positive opinion recommending its use in non-small-cell lung cancer (NSCLC) and is also considering other indications. In the US, it is licensed for use for mCRC and NSCLC, with its use as first-line treatment in mBC under review by the US FDA. In the pivotal E2100 trial in >700 previously untreated patients with locally recurrent or mBC, recipients of bevacizumab plus paclitaxel had a statistically and clinically significant increase in progression-free survival versus paclitaxel recipients (13.3 vs 6.7 months; hazard ratio 0.48; p < 0.001) [primary endpoint]. There was also a >2-fold higher objective response rate in the bevacizumab plus paclitaxel arm than in the paclitaxel arm; the between-group difference in median overall survival did not reach statistical significance (25.7 vs 23.8 months). Bevacizumab had an acceptable tolerability profile in these patients, with the majority of adverse events being generally mild to moderate in severity. There are targeted adverse events, including gastrointestinal perforations, wound healing complications and haemorrhage, which although they occur infrequently (incidence <=2%), are potentially life-threatening and may cause morbidity.
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PMID:Bevacizumab: in first-line treatment of metastatic breast cancer. 1768 75


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