When colon cancer has returned following an initial treatment with surgery, radiation therapy, and/or chemotherapy or has stopped responding to treatment, it is said to be recurrent or relapsed.
Patients with recurrent colon cancer can be broadly divided into two groups:
- Those with recurrent cancer that can be surgically removed with the goal of a cure
- Those with more widespread cancer
Colon cancer may metastasize to the liver, lung, or other locations. 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 have unresectable or widespread disease. Historically, treatment outcomes for these patients were poor. However, new combinations of chemotherapy drugs and use of targeted therapies such as Avastin® (bevacizumab), Erbitux® (cetuximab), and Vectibix® (panitumumab) have improved outcomes.
Prior to using either Erbitux or Vectibix, patients may have a sample of their cancer tested for mutations in the KRAS gene. Cancers that contain a KRAS mutation are unlikely to respond to Erbitux or Vectibix.1 2
The following is a general overview of treatment for recurrent colon cancer. Cancer treatment may consist of surgery, radiation, chemotherapy, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques--called multi-modality care--has become an important approach for increasing a patient's chance of cure and 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 influence which treatments are utilized. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. 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.
Most patients with recurrent colon cancer have previously been treated with chemotherapy; the recurrent cancer may be resistant to whatever regimen the patient has already taken. Typically, doctors will prescribe a different treatment regimen from the previous regimen.
Combination Chemotherapy: Standard treatment of advanced colon cancer generally includes chemotherapy with 5-FU. Eloxatin® (oxaliplatin) and Camptosar® (irinotecan) are chemotherapy drugs that are often added to 5-FU. Eloxatin/5-FU/LV (FOLFOX) and Camptosar/5-FU/LV (FOLFIRI) have been shown to improve survival in patients with advanced colon cancer when compared to treatment with 5-FU/LV alone.3 FOLFOX and FOLFIRI have been shown to produce similar survival benefits, but have slightly different side effects.
Targeted Therapy: 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.
Targeted therapies are often used in combination with chemotherapy, but in some cases may be used alone.
Stage IV colon cancer commonly spreads to the liver or the lungs. When metastases are limited to a single organ, treatment of that organ may improve outcomes:
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.4
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.
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 recurrent 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 recurrent 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.5 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 Karapetis CS, Khambata-Ford S, Jonker DJ et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New England Journal of Medicine. 2008;359:1757-65.
2 Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. Journal of Clinical Oncology. 2008;26:1626-1634.
3 Colucci G, Gebbia V, Paoletti G, et al. Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell'Italia Meridionale. Journal of Clinical Oncology. 2005;(23)22:4866-4875.
4 Alsina J, Choti MA. Liver-directed therapies in colorectal cancer. Seminars in Oncology. 2011;38:651-567.
5 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.