Colorectal Cancer

The treatment of colorectal cancer has undergone enormous changesin the past decade. From a disease with a single treatment option (ie,fluorouracil, a modestly effective drug), the treatment options haveevolved to include at least five new classes of antineoplastic agents.Among the considerable number of recently approved drugs, two aremonoclonal antibodies and are the testing ground for our rapidly emergingknowledge about cancer cell biology. Cetuximab (Erbitux) targetsthe epidermal growth factor receptor, an important molecule involvedwith cell cycling, survival, invasion, and metastasis. Bevacizumab(Avastin) neutralizes the vascular endothelial growth factor, blockingits ability to activate its receptor on the endothelial cells. The developmentof both antibodies resulted from decades of research in molecularand cell biology, as well as preclinical and clinical studies, and signalsa new paradigm where the tumor cells’ own unique features areexploited in a rational way.

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 past decade has given rise toan explosion of rationally designed,molecularly targetedtherapeutic agents. The epidermalgrowth factor receptor (EGFR) hasserved as the principal platform forthe development of such novel targetedtherapies, resulting in a paradigmshift in the treatment of a vast array ofsolid malignancies. Damjanov andMeropol have provided a comprehensiveand insightful overview of the roleof EGFR-directed therapeutics in colorectalcancer. They have chosen tofocus their discussion on the compoundsthat are furthest along in clinicaldevelopment and, hence, havereviewed the monoclonal antibodiescetuximab (Erbitux), ABX-EGF, andEMD 72000, as well as the small-moleculetyrosine kinase inhibitors gefitinib(Iressa) and erlotinib (Tarceva).

Damjanov and Meropol havedone an excellent job of reviewingboth the complex biologyof epidermal growth factor signalingand the current status ofepidermal growth factor receptor(EGFR, ErbB-1) inhibition for thetreatment of colorectal cancer. As theypoint out, several factors have madeEGFR a potentially high-value targetin cancer therapy. In addition, theyreview several phase II studies thathave demonstrated clinical activity foranti-EGFR antibodies in patients withadvanced colorectal cancer.

The epidermal growth factor receptor (EGFR) is commonly expressedin colorectal cancers but not in most normal tissues, raising the possibilitythat this receptor could serve as a target for highly selective therapy.Based on preclinical studies demonstrating that antagonists of EGFRresulted in the inhibition of tumor growth, the development of clinicalreagents has been aggressively pursued. Early clinical studies demonstratedantitumor activity of EGFR inhibitors in patients with advancedcolorectal cancer, with acceptable toxicity. This early success fueledrapid clinical development. In this article, we will review the currentstatus of EGFR inhibitors in the treatment of patients with colorectalcancer, in an effort to describe both how far we have come as well aswhere we need to go in optimizing this promising therapeutic approach.

ROCKVILLE, Maryland-The US Food and Drug Administration (FDA) has granted accelerated approval to Erbitux (cetuximab for injection, ImClone Systems and Bristol-Myers Squibb) for two indications in patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer. The agency approved use of the monoclonal antibody in combination with irinotecan (Camptosar) in patients who are refractory to irinotecan-based chemotherapy, and as a single agent in patients who are intolerant to irinotecan-based chemotherapy.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of some of the major advances in the management of gastrointestinalcancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinicalmanagement of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

CHICAGO-An advanced three-dimensional (3D) fly-through-reality form of virtual colonoscopy is an effective frontline screening tool for an average-risk, asymptomatic population, according to a prospective, multicenter trial. "It is accurate for finding clinically important polyps, and it is comparable in sensitivity to the accepted gold standard of conventional colonoscopy," Perry Pickhardt, MD, associate professor of radiology, University of Wisconsin, Madison, said at a press conference at the 89th Annual Meeting of the Radiological Society of North America (RSNA).

SALT LAKE CITY-Compared with patients with locally advanced rectal cancer who receive chemoradiotherapy postoperatively, those who receive chemoradiotherapy preoperatively have a downstaging of their cancer at surgery, a lower rate of local recurrence, a higher rate of sphincter preservation when tumors are low lying, and a lower rate of adverse effects, according to early results of the German Rectal Cancer Study (CAO/ARO/AIO-94). Lead author Rolf Sauer, MD, director of the Strahlenklinik, Erlangen, Germany, presented the results at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO plenary session, abstract 2).

BETHESDA, Maryland—Newly released data show that the nation’s mortality rate for all cancers combined, which declined between 1994 and 1998, remained stable from 1998 through 2000. However, the mortality rate for the four leading malignancies in the United States—lung, female breast, prostate, and colorectal—continued to decline in the late 1990s, according to the "Annual Report to the Nation on the Status of Cancer, 1975-2000."

CHICAGO-The XELOX regimen, which combines oral capecitabine (Xeloda) and oxaliplatin (Eloxatin), was safe and "highly active" in a phase II study of 35 elderly patients with advanced colorectal cancer. On behalf of the Southern Italy Cooperative Oncology Group, Pasquale Comella, MD, of the National Tumor Institute, Naples, presented the study in a poster at the 39th Annual Meeting of the American Society of Clinical Oncology (abstract 2939).