Advanced Colorectal Cancer

Treatment

Many treatment options exist to help you with your battle against advanced colorectal cancer. Surgery and radiation therapy are con-sidered local therapies because they target only the area of the tumor, while chemotherapy and targeted therapy are considered systemic treatments because the drugs travel throughout the body via the bloodstream. These types of treatment can be used alone or in combination with each other. Your doctor will select your specific treatment plan according to several factors, including the stage of your disease, the location of the tumor(s) and your overall health.

Surgery

Surgery, also called surgical resection, involves removing the tumor during an operation. The surgeon removes the area of the colon or rectum containing the tumor as well as nearby tissues and lymph nodes. If possible, the surgeon will then reconnect the healthy sections of the colon or rectum in a process called anastomosis, keeping the body’s waste-removal system operational.

Sometimes the area of anastomosis needs to be bypassed to allow more time for healing and to reduce the risk of a stool leak. This is usually done in the treatment of rectal cancer, especially after being treated with radiation and/or if the connection (or anastomosis) is close to the anal sphincter muscles. In those cases, the surgeon will create an opening in the wall of the abdomen and attach either part of the colon or part of the small intestine to the opening. This procedure is called a colostomy (if the colon is used) or ileostomy (if the small bowel is used), and the opening is called a stoma. A pouch is then attached to the skin around the stoma and is worn outside the body to collect waste; it is manually removed, emptied and reattached as necessary. An ileostomy is usually used in the treatment of rectal cancer and is temporary. However, if the anal sphincter muscles have to be removed, a permanent colostomy is performed. Colostomies are done more frequently for rectal cancers than for colon cancers. In treating rectal cancers, however, the goal is still to preserve the anal sphincter in order to retain as much normal bowel function as possible.

If your cancer has metastasized (spread) to other organs, such as the liver or the lungs, you may also have a surgical resection to re-move the tumors in those organs. If a surgical procedure cannot remove the metastatic tumor(s), other nonsurgical techniques may be used to destroy them (see Table 1). Talk to your doctor about which option might work best for you.

Table 1. Nonsurgical treatments for metastatic tumors

Radiofrequency ablation (RFA) RFA kills tumors using high-energy radio waves that travel through a thin probe inserted under the skin and into the tumor.
Ethanol (alcohol) ablation Alcohol is injected directly into the tumor to kill cancer cells.
Cryosurgery Cold gasses pass through a probe inserted under the skin and into the tumor, thereby freezing and destroying the tumor.
Hepatic artery embolization In cases of liver metastasis, materials are injected into the hepatic artery, which feeds most cancer cells in the liver, to reduce blood flow and “starve” the tumor. This procedure, however, is rarely used and usually not as effective.

 

Radiation therapy

Radiation therapy is the use of high-energy X-rays to kill cancer cells or keep them from growing. It is often used for patients with rectal cancer but is not typically used for patients with colon cancer. The type of radiation therapy used most often on rectal cancer patients is external-beam radiation therapy, which is delivered from a machine outside of the body. Radiation therapy may be used either before surgery (neoadjuvant therapy) to shrink the tumor and make it easier to remove, or after surgery (adjuvant therapy) to destroy any cancer cells that may remain.

If radiation is part of your treatment plan, a radiation oncologist will carefully plan your therapy before it begins to calculate the ap-propriate dose and determine the optimum number of treatments. The number of radiation treatments will vary according to the type and stage of your rectal cancer, but the therapy is safe and will not make you radioactive.

In addition, if your colorectal cancer has metastasized to the lung(s), brain or bones, radiation therapy may be used to destroy the metastatic tumors and/or relieve any pain they may be causing.

Chemotherapy

Chemotherapy is the use of drugs to stop the growth of cancer, either by killing cancer cells or by preventing them from dividing and growing. Because chemotherapy drugs attack all cells that divide rapidly, it may damage some normal cells, such as those lining the inside of your mouth and stomach. (See Side Effects for more information about possible side effects.)

Chemotherapy can be used for patients with Stage III or IV colon and rectal cancers. Like radiation therapy, chemotherapy may be given after surgery (adjuvant therapy) to help reduce the risk of recurrence, or before surgery (neoadjuvant therapy) to reduce the size of a tumor for patients with rectal cancer, making it easier to surgically remove. Chemotherapy may also be used as the primary treatment for disease that has spread to other organs, such as the liver or the lungs.

Chemotherapy is given in cycles, which refers to treatment on specific days over a period of time. Each cycle includes a rest period to allow your body to recover from the effects of the drugs. Several chemotherapy drugs are approved by the U.S. Food and Drug Administra-tion (FDA) to treat colorectal cancer in the United States, and these drugs are usually more effective when given in combination (See Table 2).

Table 2. Colorectal cancer drugs and combinations

FDA-approved chemotherapy drugs
capecitabine (Xeloda)
fluorouracil (Carac, Efudex, Fluoroplex)
irinotecan (Camptosar)
oxaliplatin (Eloxatin)
FDA-approved targeted therapy drugs
bevacizumab (Avastin)
cetuximab (Erbitux)
panitumumab (Vectibix)
ziv-aflibercept (Zaltrap)
Common drug combinations
fluorouracil with leucovorin (Fusilev)
fluorouracil with folinic acid and oxaliplatin; this combination is called FLOX
fluorouracil with leucovorin and oxaliplatin; this combination is called FOLFOX
fluorouracil with leucovorin and irinotecan; this combination is called FOLFIRI
capecitabine with oxaliplatin; this combination is called CapeOx
capecitabine with irinotecan
FOLFIRI with ziv-aflibercept

 

Depending on the drug, chemotherapy is given either intravenously or orally. If taken orally, you will be responsible for taking it as directed on your own, with regular medical visits so your doctor can check your progress. If your chemotherapy is an intravenous drug, it will be administered through either a vein in your arm or a port inserted into your chest. You will receive intravenous chemotherapy in a medical facility, and before each treatment session starts, a small sample of blood will be collected for laboratory tests. These tests are done to make sure that the number of different types of blood cells in your body is high enough for your body to tolerate the chemotherapy. Depending on the chemotherapy drug(s) you receive, you may also receive treatment to prevent side effects.

Chemoradiation therapy

Chemoradiation therapy refers to chemotherapy given at the same time as radiation therapy. It is especially effective for rectal cancer and may be used before surgery (neoadjuvant therapy) to help shrink the tumor, as many rectal cancers are more difficult to surgically re-move than colon cancers, or after surgery (adjuvant therapy) to reduce the risk of recurrence. The advantage of this approach is that the chemotherapy drugs make the tumor more sensitive to the radiation, so the radiation therapy is more effective.

Targeted therapy

Targeted therapy is the use of drugs that focus on blocking genes, proteins and other molecules that allow cancer to grow. Targeted therapy drugs are possible because of advances in the understanding of the genetic abnormalities and proteins responsible for the growth of different types of cancer. Like chemotherapy, targeted therapy drugs may be administered either orally or intravenously, or they may be injected. Targeted therapy is currently approved only for Stage IV colorectal cancers, which have spread to other organs (metastasized).

EGFR inhibitors

One target involved in the development of colorectal cancer is the epidermal growth factor receptor (EGFR). In colorectal cancers, an increased amount (overexpression) of the EGFR protein triggers a complex process that leads to increased growth and division of cancer cells and the spread of cancer. Targeted therapy drugs that block the activity of EGFR, thereby shrinking or stabilizing the growth of colorectal cancer, are called EGFR inhibitors. The two EGFR inhibitors approved for the treatment of metastatic colorectal cancer are cetuximab (Erbitux) and panitumumab (Vectibix).

EGFR inhibitors are effective only in tumors that do not carry mutations of the KRAS gene. Approximately 40 percent of colorectal cancers have KRAS mutations, making them immune to EGFR inhibitors; therefore, your doctor will perform KRAS screening tests before prescribing you one of these drugs. Determining your tumor’s KRAS mutation status can help you avoid unnecessary expenses and expo-sure to toxicities from EGFR inhibitors.

VEGF inhibitors

Targeted therapy drugs have also been developed to attack another pathway: the vascular endothelial growth factor (VEGF) pathway. This pathway is involved in the formation of new blood vessels (a process called angiogenesis), and the targeted therapy interferes with signals between the VEGF pathway and its receptors on the tumor’s blood vessels. As a result, no new blood vessels are formed. Without vessels to bring blood to the tumor, it “starves” and cannot continue to grow.

VEGF inhibitors are also known as anti-angiogenic drugs. The three anti-angiogenic drugs approved for use in advanced colorectal cancer are bevacizumab (Avastin), regorafenib (Stivarga) and ziv-aflibercept (Zaltrap). Bevacizumab along with chemotherapy is a first-line treatment (first treatment given); ziv-aflibercept along with FOLFIRI chemotherapy is a second-line treatment (used if the cancer progresses or recurs during or after first-line therapy); and regorafenib is used for patients who have already received certain types of chemotherapy and other targeted therapies.

The emerging use of testing for genetic mutations in colorectal tumor tissue is helping to better select patients likely to benefit from targeted therapy and is paving the way for the personalized treatment of colorectal cancer.

 

Clinical trials

Clinical trials are essential for evaluating new treatments for people with advanced colorectal cancer. They are conducted under the care of physicians and other research professionals and sponsored by government agencies, by individual doctors and health care groups, or by the pharmaceutical or biotechnology companies that developed the treatments. People who volunteer for a clinical trial gain access to new treatments before they are available to the general public and can take an active role in their own health care. To find a clinical trial that may be right for you, ask your treatment team or visit one of these online listings:

 

 

Palliative care

Supportive (palliative) care is an essential part of the overall treatment plan for people with advanced colorectal cancer. Many people mistake palliative care as care given only to people who are dying—but that is not true. The goal of palliative care is to make sure all people with cancer (or other diseases) receive care that prevents and/or relieves their pain, disease-related symptoms and side effects of treatment. It also includes supporting their emotional and social needs.

While pain is often the most feared cancer-related symptom, no one with cancer should expect to endure pain. Multiple prescription drugs can provide effective relief, and you should talk to your doctor to ensure that your pain is managed adequately, allowing you to enjoy everyday activities. Sometimes pain is caused by a tumor that blocks part of the colon or rectum. If that is the case, radiation therapy may help shrink the tumor, which will alleviate both the blockage and the pain. In addition, a surgical procedure can relieve symptoms related to blockage by either removing the tumor or inserting a stent (a small tube) to prop open the intestine. Each type of treatment is associated with side effects, which you can learn more about on the Side Effects section.

You should receive palliative care throughout your course of treatment, whether you have Stage III or Stage IV disease. If you have metastatic disease that cannot be controlled, learn more about hospice care and talk to your doctor about when hospice care may be appropriate. Most people wait too long to receive hospice care and lose the benefit of enhanced quality of life that hospice care can provide.

 

Additional Resources

 

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