Colorectal Cancer

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.

A small molecule that inhibits the insulin-like growth factor 1 receptor (IGF-1R) has blocked the development of human colorectal tumors in mice, according to researchers from OSI Pharmaceuticals, Melville, New York.

An increasing body of evidence suggests that geriatric patients can benefit from and tolerate standard chemotherapy similarly to younger patients in the settings of both early- and advanced-stage colorectal cancer. Assessment of this unique population requires more comprehensive evaluation in addition to routine history, physical examination, and laboratory tests. Specific considerations of their physiologic functional changes will help physicians better manage these patients. Ongoing studies are now designed to better understand the decision-making process, safety profile, and efficacy of various treatment regimens in geriatric patients.

Panitumumab, a new targeted treatment for advanced colorectal cancer, plus best supportive care extended progression-free survival (PFS) significantly, compared with best supportive care alone, Marc Peeters, MD, PhD, of Ghent University Hospital, Belgium, said at the 97th Annual Meeting of the American Association for Cancer Research (AACR) (abstract CP-1). FDA has granted the drug fast-track status, and it could be approved for use by the fall of this year.

A blood-based DNA test to detect colorectal cancer has the potential to increase screening rates and the number of tumors found at an early stage, according to researchers at Epigenomics, Inc. the Seattle-based molecular diagnostics company that is developing the test (see graphic on page 1).

Two large randomized trials have shown that the COX-2 inhibitor celecoxib (Celebrex) significantly reduces the recurrence of colorectal adenomas, according to data presented at the 97th Annual Meeting of the American Association of Cancer Research. However, the trials also found a significantly increased risk of serious cardiovascular (CV) events—strokes and heart attacks—among trial participants taking the drug. Celecoxib researchers and other experts at the meeting emphasized that more needs to be known about how and why celecoxib raises CV risk before it can be recommended for prevention of colorectal cancer.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.