Colorectal Cancer

Following priority review, the US Food and Drug Administration (FDA) has approved Amgen Inc's panitumumab (Vectibix) for the treatment of advanced colon cancer.

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.

For metastatic colorectal cancer, the benefits of maintenance therapy with 5-FU/leucovorin appear questionable, according to results of the OPTIMOX2 study

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.

In patients with resectable rectal cancer, routine short-course preoperative radiotherapy results in a significant reduction in local recurrence and improved disease-free survival, compared with a selective postoperative approach.

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.

Preoperative chemotherapy with FOLFOX4 reduces by almost one-third the sum of the diameters of potentially resectable liver metastases of colorectal cancer

Roche has reported that a large international phase III study (NO16966) enrolling 2,035 patients with previously untreated metastatic colorectal cancer (CRC), met both primary endpoints

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.

In a phase III study, patients with untreated metastatic colon cancer had significantly higher response rates when cetuximab (Erbitux) was added to their chemotherapy, compared with chemotherapy alone (FOLFIRI or FOLFOX)

FOLFIRI can be given intermittently in advanced previously untreated colorectal cancer, with survival rates and toxicity similar to continuous FOLFIRI

Percutaneous radiofrequency ablation (RFA) of lung metastases of colorectal cancer may be a useful treatment option in patients who are not candidates for surgery, but the benefit varies with the size of the metastases

A phase I trial finds that the combination of cetuximab (Erbitux) and gefitinib (Iressa) produces responses in patients with advanced solid cancers expressing the epidermal growth factor receptor (EGFR)—especially colorectal cancer.

Current evidence suggests that colonoscopy screening can reduce mortality from colorectal cancer—if these procedures are performed in a high-quality manner, David A. Lieberman, MD, said at the 2006 Gastrointestinal Cancers Symposium.

People with hereditary nonpolyposis colorectal cancer (HNPCC), are willing to consider the pros and cons of prophylactic subtotal colectomy to manage their disorder, but still have strong concerns about the procedure

Increasing patient comfort may translate into higher screening rates for colon cancer, researchers said at Digestive Disease Week 2006. A new colonoscopy system promises a gentler procedure (abstract 719) and an alternative sedation method allows a quicker recovery time (abstract 645).

Avastin (bevacizumab, Genentech), in combination with FOLFOX4-oxaliplatin (Eloxatin)/5-FU/leucovorin—has received FDA approval for the second-line treatment of metastatic colorectal cancer.

In trials of first-line chemotherapy for metastatic colorectal cancer, gains in progression-free survival (PFS) are a good surrogate endpoint for gains in overall survival (OS), according to results of a study presented by Patricia A. Tang, MD, at the 2006 Gastrointestinal Cancers Symposium (abstract 226).

Genentech Inc, recently announced that the US Food and Drug Administration (FDA) approved bevacizumab (Avastin) in combination with intravenous fluorouracil (5-FU)-based chemotherapy for second-line metastatic colorectal cancer.