Colon and Rectal Cancers - Medications

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In a study of 800 patients with metastatic colorectal cancer, bevacizumab administered intravenously along with IFL extended survival by approximately 5 months longer than IFL alone. Common side effects of bevacizumab are nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).

Cetuximab. Cetuximab (Erbitux) was approved in February 2004 for the treatment of metastatic colorectal cancer. This monoclonal antibody drug targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan, or alone for patients who have not responded to irinotecan. Clinical research demonstrated that combination treatment delayed tumor growth by 4 months. For patients who received only cetuximab, tumor growth was delayed by 1.5 months.

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Side Effects of Chemotherapy

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, anticancer drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles.

Side effects vary specifically with different drugs, but, in general, they include the following:

• Nausea and vomiting. Drugs are available to significantly reduce these dreaded side effects. Serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs, and most patients who take more powerful drugs. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting.
• Diarrhea (very common with 5-FU)
• Temporary hair loss (usually minimal with 5-FU)
• Weight loss
• Mouth ulcers
• Pain and redness of the hands and feet
• Fatigue
• Anemia
• Depression

These side effects are nearly always temporary, and medications are available to help manage them. Most patients are able to continue with normal activities for all but perhaps 1 - 2 days a month.

More serious complications can also occur and may vary depending on the specific drugs used. They include:

• Increased chance for infection (from suppression of the immune system)
• Bleeding

Targeted Therapies and Biologics

One of the most promising recent developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapeutic drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotype. In the future, diagnostic tests may help doctors identify which patients are more likely to respond successfully to specific drugs.

Biologic therapies use the body's immune system to attack the cancer (immunotherapy). These drugs are derived from biological sources and include vaccines, monoclonal antibodies (MAbs), and gene therapies. Many targeted therapies are classified as biologics.

Targeted therapies involve many different types of drugs and molecular pathways. These include:

Angiogenesis Inhibitors. Anti-angiogenesis drugs inhibit the formation of new blood vessels that supply tumors with the blood, oxygen, and nutrients vital to tumor growth. Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin), target vascular endothelial growth factor (VEGF).

Tumor Growth Factor Inhibitors. Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Drugs that target the epidermal growth factor receptor (EGFR) include the recently approved cetixumab (Erbitux). Panitumumab is another monoclonal antibody showing promise in treating patients with metastatic colorectal cancer.

Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. Clinical trials are currently investigating the use of the lung cancer drug gefitinib (Iressa), in combination with oxaliplatin and standard chemotherapy drugs, for the treatment of advanced colorectal cancer. Gefitinib blocks tyrosine kinase growth signaling capacities. Similarly, the EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is in late-stage trials for the treatment of pancreatic and lung cancer, is also being investigated as an adjuvant treatment for metastatic colorectal cancer.

Vaccines. ALVAC is an experimental vaccine derived from the canarypox virus. It is designed to trigger the body's immune system to fight cancer cells. It is currently in early-stage clinical trials to determine its efficacy in combination with chemotherapy for treatment of metastatic colorectal cancer.

Review Date: 03/06/2007
Reviewed By: A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (9/1/2006).