Colorectal Cancer

Targeting the epidermal growth factor receptor (EGFR) has proven to be of clinical benefit in the management of metastatic colorectal cancer (mCRC). While the use of small-molecule tyrosine kinase inhibitors in this setting has not shown any significant activity and has been associated with increased gastrointestinal toxicity when combined with chemotherapy, a different picture has emerged with the use of EGFR-targeting monoclonal antibodies.

Cetuximab (Erbitux) plus best supportive care (BSC) provided significantly better overall survival and progression-free survival, compared with BSC alone, in patients with advanced colorectal cancer who had failed or could not take all approved chemotherapies

multicenter, open-label, randomized phase III trial recently published in the New England Journal of Medicine (357:2040-2048, 2007) demonstrated that cetuximab (Erbitux) as a single agent significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to approved chemotherapy agents.

US Food and Drug Administration (FDA) has granted an expanded clearance for the CellSearch System to be used as an aid in the monitoring of metastatic colorectal cancer

10 notable developments and events in cancer research and care

A growing number of novel antiangiogenic agents are entering clinical trials to study their clinical safety and efficacy. A few, such as bevacizumab (Avastin), sorafenib (Nexavar), and sunitinib (Sutent), have received US Food and Drug Administration approval and are already in widespread clinical use. As knowledge about the intricacies of intracellular signaling within multiple tumor types expands, agents with the capacity to impact these pathways are being incorporated into additional clinical trials alone and in combination with other targeted and/or traditional antineoplastic agents. Early clinical trials have focused on highly vascular tumor types, as well as those known to significantly overexpress the VEGF (vascular endothelial growth factor) receptor family. This article aims to review the status of antiangiogenic therapy in selected tumor types and discuss areas for further research.

Compared with optical colonoscopy, CT colonography achieves similar outcomes with a fraction of the number of polypectomies

This 47-year-old man underwent surveillance colonoscopy for a history of an adenomatous polyp. He has a history of hemorrhoids and occasional bright red blood on the toilet tissue. There is no history of diarrhea, constipation, or abdominal pain.

FDA has approved a supplemental biologics license application for ImClone and Bristol-Myers Squibb's Erbitux (cetuximab) to add monotherapy survival data to the agent's labeling

The notion of "lines" of therapy for treatment of patients with colorectal cancer appears to be blurred, with the actual sequence of treatment becoming less important than making sure patients have access to all active agents, Axel Grothey, MD, of the Mayo Clinic, said at the Third Annual Oncology Congress

New animal studies show that the loss of two hormones plays a significant role in the development of colon cancer. If confirmed, the discovery "converts colon cancer from a genetic disease, which is the way we've all thought about it, to a disease of hormone insufficiency,"

Cancer in the proximal colon, the right part of the colon closest to the small intestine, has been increasing in African-American men since the mid-1990s.

A gene-based therapeutic cancer vaccine given along with standard chemotherapy produced tumor shrinkage in 6 of 11 evaluable patients with metastatic colorectal cancer. Results of the phase II trial

This photograph is from an upper gastrointestinal endoscopy on a 15-year-old male. He has a history of a total colectomy and is being evaluated for iron deficiency anemia. He denies abdominal pain, weight loss, and melena. He notes occasional bright red blood on the toilet paper but denies hematochezia.

A 72-year-old man is referred for evaluation of abnormal liver chemistries. He has a history of unresectable pancreatic cancer (adenocarcinoma of the head).

Interim results of a phase I/II trial of NV1020, an oncolytic herpes simplex virus (HSV), in refractory metastatic colorectal cancer patients are encouraging

Amgen is currently enrolling patients in a phase III study designed to evaluate the effectiveness of panitumumab (Vectibix) in combination with chemotherapy (FOLFIRI)

Nanoparticle albumin-bound (nab) rapamycin (ABI-009) showed antitumor activity in xeno-graft models of breast and colon cancer, according to investigators from Abraxis BioScience

Capsule endoscopy may eventually rival colonoscopy for the detection of colon polyps, according to the leaders of an ongoing clinical trial comparing the two technologies.

Integrins have direct effects in stimulating proliferation and preventing apoptosis in cancer cells and mediating proangiogenic interactions between endothelial cells and extracellular matrix. Alterations of expression of various integrins and their receptors have been observed in various cancers in which angiogenesis is known to play a role, including colorectal cancer. Inhibition of specific integrins might thus inhibit both direct effects of integrins on cancer cells and tumor angiogenesis. Inhibitory peptides and anti-integrin monoclonal antibodies are currently being investigated in clinical trials in patients with solid tumors, with early evidence suggesting clinical benefit in disease stabilization with use of an anti-αvβ3 antibody in the settings of colorectal cancer, renal cell carcinoma, and melanoma. Integrin inhibition alone and with other targeted therapeutic approaches should be further investigated in clinical trials in patients with colorectal cancer.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.

In an ongoing phase I trial in patients with solid tumors and lymphomas, the small-molecule tumor vascular disrupting agent NPI-2358 (Nereus Pharmaceuticals, San Diego, California) was dose escalated without evidence of dose-limiting toxicity

FOLFOX4 given before and after resection of colorectal cancer liver metastases can significantly reduce the risk of recurrence, according to final data from the first study to test this approach.

"In patients with metastatic colorectal cancer (mCRC), the number of circulating tumor cells (CTCs) before and after initiation of treatment is a significant independent predictor of progression-free survival and overall survival," Neal J. Meropol, MD, reported

Patients with stage III colon cancer who have undergone surgery and chemotherapy with curative intent may have a higher risk of relapse and death if they follow a predominantly "Western" diet

Monoclonal antibodies to the epidermal growth factor receptor (EGFR) are among the promising novel targeted therapies being explored in colorectal cancer. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). This review will address the use of cetuximab and panitumumab in chemotherapy-refractory colorectal cancer as well as in front-line therapy for the disease, consider predictors of response and resistance, and outline comparisons between these agents.

The US Food and Drug Administration (FDA) has accepted, for filing and priority review, the New Drug Application (NDA) for Bristol-Myers Squibb's investigational compound ixabepilone, an epothilone B analog.

Monoclonal antibodies to the epidermal growth factor receptor (EGFR) are among the promising novel targeted therapies being explored in colorectal cancer. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). This review will address the use of cetuximab and panitumumab in chemotherapy-refractory colorectal cancer as well as in front-line therapy for the disease, consider predictors of response and resistance, and outline comparisons between these agents.

Monoclonal antibodies to the epidermal growth factor receptor (EGFR) are among the promising novel targeted therapies being explored in colorectal cancer. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). This review will address the use of cetuximab and panitumumab in chemotherapy-refractory colorectal cancer as well as in front-line therapy for the disease, consider predictors of response and resistance, and outline comparisons between these agents.

People who have had adenomas removed during colonoscopy are returning for surveillance colonoscopies more frequently than recommended by current guidelines