Richard M. Goldberg, MD

Every year in the United States, approximately 160,000 cases of colorectal cancer (CRC) are diagnosed, and about 57,000 patients die of the disease, making it the second leading cause of death from cancer among adults.

In this ASCO podcast, Dr. Goldberg, Distinguished Professor, Hematology/Oncology, at the University of North Carolina Lineberger Comprehensive Cancer Center and the Physician-in-Chief of the North Carolina Cancer Hospital, spoke about the new developments in advanced colorectal cancer since his ASCO 2003 practice-changing presentation.

Infusion reactions (IRs) can be broadly categorized by their immunologic mechanism. Anaphylaxis is a systemic, immediate hypersensitivity reaction mediated by factors released from interactions between immunoglobulin E (IgE) and mast cells that produce an antigen-antibody reaction.[1] Anaphylactoid reactions can be differentiated from anaphlaxis by the fact that they are not IgE-mediated but rather cytokine-mediated.

Colorectal cancer is the third most common cancer in the United States.[1] In 2008, an estimated 148,810 new cases of colorectal cancer will be diagnosed and nearly 50,000 people will die of the disease.

Taken together, the results of the C-07 and MOSAIC trials suggest that oxaliplatin improves both disease-free and overall survival in this population [resected stage II-III colon cancer patients], said Dr. Goldberg, of the University of North Carolina Lineberger Comprehensive Cancer Center.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

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.

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.

During the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise in fighting colorectal cancer.

Because of recent advances ineach discipline we commonlyrecommend and deliver threemodalities-chemotherapy, radiation,and surgery-in the management oflocalized gastrointestinal cancers inpatients who are judged to be suitablecandidates for aggressive therapy.After years of experimentation andsome therapeutic misadventures, combinationchemotherapy can now bedelivered with greater safety and effectiveness.This is based in part onbetter antiemetics, better supportivetherapies such as judicious use of granulocytecolony-stimulating factors,and more accurate models for adjustingdosages based on pharmacokineticand pharmacodynamic profiling.

Colorectal cancer is the second most common cause of cancerrelateddeath in the United States. Approximately 30% to 40% of patientswith colorectal cancer have locoregionally advanced or metastaticdisease on presentation and cannot be cured with surgical therapy.After many years without significant change, systemic therapy forcolorectal cancer is rapidly evolving. The past decade has seen the introductionof new chemotherapeutic agents such as irinotecan(Camptosar), oxaliplatin (Eloxatin) and the oral 5-FU prodrugcapecitabine (Xeloda). Combination studies of these new agents withthe standard 5-FU/leucovorin have extended median survival in patientswith advanced colorectal cancer for up to 21 months. In addition,targeted agents with activity in colorectal cancer have emergedand are promising. This article reviews the current treatment recommendationsfor patients who present with advanced colorectal cancer.Survival in patients with advanced colorectal cancer is on a positivetrajectory. The hope that some patients with advanced disease will belong-term survivors (even without surgery) appears to be within therange of possibility.

The current recommendation for adjuvant chemotherapy for patients with newly diagnosed stage III colon cancer involves 6 months of fluorouracil (5-FU) plus low- or high-dose leucovorin. In clinical trials performed throughout

One of the more promising chemotherapeutic agents for patients with metastatic colorectal cancer is oxaliplatin (Eloxatin), a third-generation platinum derivative with a unique mechanism of action. Preclinical studies

The article by Damjanov and Meropol elegantly outlines the rationale behind the preclinical development of several potential new oral chemotherapy options for patients with advanced colorectal carcinoma and the available data from clinical trials in advanced colorectal cancer that evaluated the activity and safety of these agents. The authors relate the history of fluorinated pyrimidine therapy in colorectal cancer and the pharmacologic challenges to delivering effective oral therapy in a such a way that the chemistry behind the processes becomes readily intelligible. They note that the erratic absorption and blood levels associated with orally administered fluorouracil (5-FU) led to the current approaches to oral therapy.

The article by Drs. Peeters and Haller provides the details of 20 years of investigation into the adjuvant therapy of colorectal cancer. The authors describe pivotal trials through which an international cast of investigators have identified adjuvant

Both fluorouracil (5-FU) and irinotecan (CPT-11 [Camptosar]) have shown activity in metastatic colorectal cancer and are approved for its treatment in the United States. Preclinical experiments in cell cultures and human tumor