Colon cancer is classified as Stage IV if the final evaluation following surgical removal of the cancer shows that the cancer has spread to distant locations in the body; this may include the liver, lungs, bones, distant lymph nodes or other sites. While it is commonly thought that patients diagnosed with Stage IV colon cancer have few treatment options, certain patients can still be cured of their cancer, and others can derive significant benefit from additional treatment.
Patients with Stage IV colon cancer can be broadly divided into two groups:
- Those with widespread, metastatic cancer that cannot be treated with surgery (sometimes called unresectable cancer )
- Those with cancer that has metastasized to a single site
When the site of metastasis is a single organ (such as the liver), and the cancer is confined to a single defined area within the organ, patients may benefit from local treatment directed at that single metastasis.
The majority of patients diagnosed with Stage IV colon cancer have unresectable or widespread disease. Historically, treatment outcomes for these patients were poor. However, new combinations of chemotherapy drugs and the addition of targeted therapies such as Avastin® (bevacizumab) have improved outcomes.
The following is a general overview of treatment for Stage IV colon cancer. Treatment may consist of surgery, radiation, chemotherapy, targeted therapy, or a combination of these treatment techniques. Multi-modality treatment, which is treatment using two or more techniques, has become an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied.
The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
This section covers the initial, also called first-line, treatment of Stage IV colon cancer. For information about the treatment of cancer that has recurred or progressed after initial treatment, visit Recurrent Colon Cancer.
Chemotherapy for Widespread, Metastatic Colon Cancer
For over 30 years the chemotherapy drug fluorouracil (5-FU) was the standard treatment for metastatic Stage IV colon cancer that had spread to several sites in the body. 5-FU is typically administered with leucovorin, a drug that is similar in structure and function to the essential vitamin folic acid. Leucovorin (LV) enhances the anticancer effects of fluorouracil by helping the chemotherapy drug bind to and stay inside the cell for a greater period of time, producing longer lasting anticancer effects.
More recently, the addition of other drugs to 5-FU/LV has been found to provide additional benefit. Not all patients can tolerate these multi-drug regimens, however, and less intensive regimens are available.
Adding Targeted Therapy to Chemotherapy
Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy. Recently approved targeted therapies represent the most novel advance in the treatment of metastatic colorectal cancer in the last few years.
Targeted therapies that have shown a benefit for selected patients with metastatic colorectal cancer include Avastin® (bevacizumab), Erbitux® (cetuximab), and Vectibix® (panitumumab). Avastin blocks a protein (VEGF) that plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Erbitux and Vectibix slow cancer growth by targeting a protein known as EGFR. Cancers with certain gene mutations are unlikely to respond to Erbitux or Vectibix, and tests are available to detect these mutations before treatment decisions are made.
Treatment of Colon Cancer That has Metastasized to a Single Site
Stage IV colon cancer commonly spreads to the liver or the lungs. Some patients who have cancer that has spread to a single area are candidates for surgery to remove the metastases.
Treatment of the liver: When it’s possible to completely surgically remove all liver metastases, surgery is the preferred treatment. Although surgery offers some patients the chance for a cure, a majority of patients with liver metastases are not candidates for surgery because of the size or location of their tumors or their general health. Some of these patients may become candidates for surgery if initial treatment with chemotherapy shrinks the tumors sufficiently. If the tumors continue to be impossible to remove surgically, other liver-directed therapies may be considered. These other therapies include radiofrequency ablation (use of heat to kill cancer cells), cryotherapy (use of cold to kill cancer cells), delivery of chemotherapy directly to the liver, and radiation therapy. Relatively little information is available from clinical trials about the risks and benefits of these other approaches, but they may benefit selected patients.1
Treatment of the Elderly
A large percentage of patients with advanced colorectal cancer are 65 years or older. Because elderly patients commonly have concurrent illnesses or other medical difficulties that are perceived to exacerbate the side effects of chemotherapy, elderly patients are often treated with reduced doses of chemotherapy. Clinical studies have shown, however, that elderly patients get the same benefit from chemotherapy treatment as younger patients.
While a dose reduction or delay may sometimes be necessary, it may also compromise the optimal treatment of some patients. All patients over 65 should be closely monitored for toxic side effects of chemotherapy, especially during their initial chemotherapy administration cycle.
Strategies to Improve Treatment of Stage IV Colon Cancer
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage IV colon cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of Stage IV colon cancer include the following:
New Approaches to Treating Liver Metastases: Researchers continue to explore news ways to treat cancer that has spread to the liver. One approach that is being evaluated is radioembolization This strategy uses radioactive microspheres (small spheres containing radioactive material). The small spheres are injected into vasculature of the liver, where they tend to get lodged in the vasculature responsible for providing blood and nourishment to the cancer cells. While lodged in place, the radioactive substance spontaneously emits radiation to the surrounding cancerous area while minimizing radiation exposure to the healthy portions of the liver.2 Researchers are also exploring alternatives to radiofrequency ablation for the destruction of liver tumors, as well as new approaches to delivering chemotherapy to the liver.
New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research.
New Approaches to Targeted Therapy: Targeted therapies such as Avastin, Erbitux, and Vectibix already play a role in the treatment of selected patients with advanced colorectal cancer, but researchers continue to explore new targeted therapies as well as new ways of using existing drugs. Developing tests to predict which patients are most likely to respond to which drugs is also an important focus of research. Tests to identify certain gene mutations in the cancer are already available, and can help guide the use of Erbitux and Vectibix.
Managing Side Effects: Techniques designed to prevent or control the side effects of cancer and its treatments are called supportive care. Side effects not only cause patients discomfort, but also may prevent the delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that treatment is delivered as planned and that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.
Phase I clinical trials: New chemotherapy drugs continue to be developed and evaluated in patients with recurrent cancers in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the best way of administering the drug and whether the drug has any anticancer activity in patients.
1 Alsina J, Choti MA. Liver-directed therapies in colorectal cancer. Seminars in Oncology. 2011;38:651-567.
2 Hendlisz A, Van den Eynde M, Peeters M, et al. Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy. Journal of Clinical Oncology. 2010;28:3687-94.