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Colorectal Cancer

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Adding the targeted antibody cetuximab (Erbitux) to standard cytotoxic chemotherapy as first-line treatment for patients with advanced colorectal cancer improves response rates, two groups of researchers said at the 31st Congress of the European Society for Medical Oncology (ESMO).

A phase III trial has shown that XELOX is as effective as FOLFOX4 in patients with metastatic colorectal cancer, and that adding the targeted agent bevacizumab (Avastin) to either regimen improves progressionfree survival (PFS).

The science supporting molecularly targeted therapies for the treatment of patients with solid tumors continues to evolve. Nurses are challenged to understand cell signaling, molecular targeting, and the mechanism of action of targeted agents. Two cell signal transduction pathways regulate the development, proliferation, and metastasis of solid tumors: the human epidermal growth factor (HER) receptor pathway and the vascular endothelial growth factor (VEGF) receptor pathway. Several novel pharmacologic agents with distinct indications and methods of administration target the HER and VEGF molecular pathways.

Novel Molecular Therapies

a brief overview of the dosing and administration guidelines for the various targeted therapy agents discussed in this supplement to the ONCOLOGY Nurse Edition. Please consult the manufacturer's package insert for more information.

The US Food and Drug Administration (FDA) has approved Amgen's Vectibix (panitumumab) for the treatment of patients with colorectal cancer that has metastasized following standard chemotherapy.

MediGene AG has announced that the interim analysis of a phase I/II trial of its oncolytic herpes simplex virus NV1020 has shown efficacy for the treatment of liver metastases in patients with colorectal cancer. Therefore, the trial will continue as scheduled, with the maximum dosage of the virus. The agent is delivered to the liver at weekly intervals through the hepatic artery. All patients receiving the maximum dosage demonstrated either disease stabilization or a clear regression of liver metastases, the company said in a press release, adding that some patients showed regressing metastases in other organs as well.

A new bioengineered protein that targets two apoptosis receptors produced one dramatic tumor regression and stopped tumor growth in several cases of disease stabilization in 60% of the advanced cancer patients treated in a phase I dose-finding trial

A polymorphism that reduces the hepatic metabolism of irinotecan (Camptosar) and that is present in about half of patients with colorectal cancer affects their odds of response to and toxicity from regimens containing this agent

Colorectal cancer is the second leading cause of cancer-related death (after lung/bronchus cancer) in the United States.[1] In 2002, a total of 139,534 adults in the United States had colorectal cancer diagnosed, and 56,603 died. The US Preventive Services Task Force and other national organizations recommend that adults aged ≥ 50 years be screened for colorectal cancer with one or more of the following tests: fecal occult blood testing (FOBT) every year, sigmoidoscopy or double-contrast barium enema every 5 years, or colonoscopy every 10 years.

Cetuximab (Erbitux), a chimeric antiepidermal growth factor receptor monoclonal antibody currently used to treat metastatic colorectal cancer, is in clinical development for several other solid tumors. Although cutaneous manifestations are the most common toxicities associated with cetuximab, they are rarely life-threatening. Cetuximab-related infusion reactions are less common, but they may become severe and cause fatal outcomes if not managed appropriately. Little about the specific etiology of these events is known; however, an overview of infusion reactions observed with other compounds may shed some light and help characterize cetuximab-related reactions. For physicians administering cetuximab, familiarity with acute reaction treatment protocols and preparedness to identify and manage symptoms promptly and effectively are most important to minimize potential risks.

Chemotherapy may render some liver metastases of colorectal cancer no longer visible by preoperative CT and ultrasound imaging (see also article on page 21), but viable cancer cells are still present in about four in five of these sites.

Colorectal cancers that do not express epidermal growth factor receptor (EGFR) may still have overactivation of the EGFR signaling pathway, new data show. In addition, activation of the signaling pathway in the primary tumor is not a reliable indicator of its activation in metastases.

Although most American adults can identify mammography, the Pap test, and colonoscopy as cancer screening tests, they are generally ill informed about the age at which screening should begin and how often they should undergo the examinations.

Nearly 150,000 people will be diagnosed with colorectal cancer in the United States in 2006. The impact of this diagnosis will be felt by countless family members, coworkers, and friends. Although screening tests for colorectal cancer have been available and encouraged by medical associations such as the American Cancer Society (ACS) and others, public awareness and compliance has been dismal.

The liver is a frequent site of metastatic colorectal disease. Over the past 20 years, improvements in systemic chemotherapy and surgical techniques have improved the survival of patients with hepatic metastases. For 4 decades, fluorouracil and leucovorin were the only drugs available to treat metastatic colorectal cancer, but several new drugs and a variety of novel regimens are now available. Further improvements in results have been seen with the delivery of chemotherapy via the hepatic artery. Surgical resection of liver metastases has been encouraged when possible, and recent advances in surgery such as portal vein embolization, have made liver resection a possibility for more patients. This review considers the timing and sequence of chemotherapy and surgery in this setting, as well as the roles of cryoablation, radiofrequency ablation, and radiation therapy.

The liver is a frequent site of metastatic colorectal disease. Over the past 20 years, improvements in systemic chemotherapy and surgical techniques have improved the survival of patients with hepatic metastases. For 4 decades, fluorouracil and leucovorin were the only drugs available to treat metastatic colorectal cancer, but several new drugs and a variety of novel regimens are now available. Further improvements in results have been seen with the delivery of chemotherapy via the hepatic artery. Surgical resection of liver metastases has been encouraged when possible, and recent advances in surgery such as portal vein embolization, have made liver resection a possibility for more patients. This review considers the timing and sequence of chemotherapy and surgery in this setting, as well as the roles of cryoablation, radiofrequency ablation, and radiation therapy.

Amgen announced interim results from two phase II studies of panitumumab, an investigational fully human monoclonal antibody that targets the epidermal growth factor receptor (EGFR). Results from both studies suggest that the antitumor activity of panitumumab was independent of tumor EGFR expression levels in patients with metastatic colorectal cancer who have failed standard chemotherapy.

The liver is a frequent site of metastatic colorectal disease. Over the past 20 years, improvements in systemic chemotherapy and surgical techniques have improved the survival of patients with hepatic metastases. For 4 decades, fluorouracil and leucovorin were the only drugs available to treat metastatic colorectal cancer, but several new drugs and a variety of novel regimens are now available. Further improvements in results have been seen with the delivery of chemotherapy via the hepatic artery. Surgical resection of liver metastases has been encouraged when possible, and recent advances in surgery such as portal vein embolization, have made liver resection a possibility for more patients. This review considers the timing and sequence of chemotherapy and surgery in this setting, as well as the roles of cryoablation, radiofrequency ablation, and radiation therapy.