Colorectal Cancer
Types of Treatment
Surgery, chemotherapy, targeted therapy and radiation therapy are options for treating colorectal cancer with a goal of cure or prolonged survival. A specific treatment plan is selected according to several factors, such as the stage of disease, the location of the tumor and the person’s overall health. Another essential component of your treatment plan is supportive (palliative) care. The focus of supportive care is managing symptoms related to the disease itself as well as the side effects of treatment.
An overview of the types of treatment that may be used for colorectal cancer is provided in this section. You will also find more information about treatment options according to specific stages of disease later in this section.
Treatment-Related Words You Should Know
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Term |
Definition |
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Ablation |
Procedure done to destroy a metastatic tumor. |
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Adjuvant therapy |
Treatment given after the primary therapy, to help prevent recurrence. |
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Anastomosis |
Surgical connection of the two ends of the colon after removal of a portion of the colon. |
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Bolus |
A single dose of a drug injected into a blood vessel over a short period of time. Fluorouracil can be given as either a bolus or as an infusion over a longer period of time. |
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Chemoradiation therapy |
The use of both chemotherapy and radiation therapy for either adjuvant or neoadjuvant treatment. |
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Cytotoxic |
Type of drug that kills cells in the body. |
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First-line therapy |
Treatment given initially for metastatic cancer; if there is no response to treatment, another chemotherapy drug can be tried (referred to as second-line therapy). |
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Inoperable |
Unable to treat with a surgical procedure, either because of the stage or location of the disease or a person’s health status; also known as unresectable. |
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Local therapy |
Treatment that is directed at the site of the tumor; surgery and radiation therapy are local therapies. |
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Neoadjuvant therapy |
Treatment given before the primary therapy, usually before an operation, to help shrink the tumor. |
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Primary therapy |
Treatment given with the intention to cure or to prolong survival. |
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Progression (disease) |
Advancement of disease; disease that becomes more extensive. |
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Refractory (disease) |
Cancer that does not respond to treatment. |
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Resection |
Surgical removal. |
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Surgical candidate |
A person for whom a surgical procedure is appropriate (the tumor can be removed safely and the surgical risks are acceptable). |
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Systemic therapy |
Treatment with chemotherapy or targeted therapy; the drugs travel throughout the body via the bloodstream after being given in a vein or by mouth. |
Surgery
Surgery is the most common treatment for both colon and rectal cancer and is usually considered the primary treatment for early stages (I and II) of the disease. It is also used in combination with chemotherapy and/or radiation therapy (for patients with rectal cancer) if lymph nodes are involved and may be used in some patients in whom the disease has spread to distant organs. The goal of surgery is to remove all of the tumor while sparing as much healthy tissue as possible. Several types of surgical procedures may be done, depending on where the tumor is located and on the clinical stage (Table 1). As already noted, finding an expert and experienced surgeon is very important.
If colon or rectal cancer is confined to a polyp or is at a very early stage, removal of the polyp (polypectomy) during colonoscopy may be sufficient treatment. If the pathologist finds cancer cells in the base of the polyp (where it was attached to the wall of the colon), the portion of the colon where the polyp was located may need to be removed to make sure that no cancer cells remain in the body. Almost all patients should have a surgical procedure that includes removal of nearby lymph nodes so that the pathologist can examine them for signs of cancer cells and determine the final stage of disease. Experts recommend that at least 12 lymph nodes be removed and then evaluated by a pathologist.
A surgical procedure for colon or rectal cancer may be done as a traditional open operation, in which large incisions are made, or as a minimally invasive operation, in which smaller incisions are made. Minimally invasive operations are laparoscopic assisted and robotic assisted procedures. You and your doctors will consider many factors in deciding which type of operation is best for you. These newer techniques are quite specialized and require the skills of an experienced and highly trained surgeon.
When a section of the colon or rectum is removed, the surgeon can usually reattach the healthy ends to each other during the same operation. This surgical reconnection is called an anastomosis. Sometimes the area of anastomosis needs to be bypassed to allow more time for healing and to reduce the risk of a leak of stool. 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 an ostomy, and the opening is called a stoma. An ostomy is done more frequently as part of treatment for rectal cancer than for colon cancer. A pouch is attached to the skin around the stoma to collect waste. Most of the time, an ostomy is temporary, but if the anal sphincter muscles have to be removed, the colostomy is permanent. In treating rectal cancers, the goal is to preserve the anal sphincter in order to retain as much normal bowel function as possible.
A surgeon who is experienced in performing operations to remove colon and/or rectal cancers should review your history and clinical findings to determine if you are a surgical candidate. Some people are not surgical candidates because their overall health makes it too great a risk to perform a surgical procedure, or less often, because the tumor is considered to be inoperable. Other treatment options are available for people who are not surgical candidates.
Chemotherapy
Chemotherapy is the use of drugs, known as cytotoxic drugs, to stop the growth of cancer, either by killing cancer cells or by preventing them from dividing and growing. Chemotherapy is sometimes referred to as conventional chemotherapy to distinguish it from targeted therapy, which also involves the use of drugs that travel throughout the body. Chemotherapy drugs attack all cells that divide rapidly, which means that the drugs may damage some normal cells, such as those lining the inside of your mouth and stomach and your bone marrow, the spongy inside of your bone where blood cells grow.
Chemotherapy is typically used for stage III and IV colon cancer and stage II, III and IV rectal cancer. As part of treatment for colon cancer, chemotherapy may be given as postoperative (adjuvant) treatment, or treatment given after an operation, to help reduce the risk of recurrence. Adjuvant chemotherapy may also be used for rectal cancer. In addition, chemotherapy can be used as preoperative (neoadjuvant) treatment, or treatment given before an operation. The purpose of neoadjuvant chemotherapy is to reduce the size of a tumor to make it easier to surgically remove. When neoadjuvant chemotherapy is used for rectal cancer, the treatment is usually combined with radiation therapy, a combination often referred to as chemoradiation therapy. The advantage of this approach is that the chemotherapy drugs make the tumor more sensitive to the radiation, so radiation therapy is more effective. Lastly, chemotherapy may be used as the primary treatment for disease that has spread to other organs, such as the liver or lungs (metastatic disease).
Several chemotherapy drugs are used to treat colon and rectal cancer, and the drugs are usually more effective when given in combination (Table 2). Chemotherapy is given intravenously, either through a vein in your arm or through a small catheter, called a port that is inserted in the upper part of your chest. You may receive intravenous chemotherapy in your doctor’s office, an outpatient infusion center or a hospital. 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 drugs. Depending on the chemotherapy drug(s) you receive, you may also receive treatment to prevent side effects.
Chemotherapy is given in cycles, which refers to treatment on specific days over a period of time. Each cycle is followed by a rest period, to allow your body to recover from the effects of the drugs.
Targeted Therapy
Targeted therapy is also treatment with drugs, but with this type of therapy, the drugs are focused on blocking 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 the proteins responsible for the growth of different types of cancer.
One target involved in the development of colorectal cancer (and other cancers) 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 are called EGFR inhibitors. Two EGFR inhibitors are approved for the treatment of metastatic colorectal cancer (Table 2).
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, and the targeted therapy interferes with signals between VEGF and its receptors that are present on blood vessels. As a result, no new blood vessels are formed. Without vessels to bring blood to the tumor, it cannot continue to grow. One VEGF inhibitor is approved for use in advanced colorectal cancer. (Table 2). VEGF inhibitors are also known as antiangiogenic drugs. This targeted therapy drug may not be appropriate for everyone because some potential side effects can be serious (such as high blood pressure, increased risk of bleeding and decreased wound healing).
Targeted therapy is currently approved only for colorectal cancer that has metastasized. To date, studies have shown that targeted therapy is not beneficial for earlier stage colorectal cancer.
The emerging use of testing for genetic mutations in colorectal tumor tissue is helping to better select patients who are likely to benefit from targeted therapy and is paving the way for personalized treatment of colorectal cancer.
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As technology has allowed for tumor tissue to be tested for genetic mutations, researchers have discovered some mutations that play an important role in the development of colorectal cancer and that influence how the tumor will respond to treatment. Testing for genetic mutations in tumor tissue is helping doctors to provide personalized treatment of colorectal cancer. Personalized cancer treatment is therapy that is selected according to the specific characteristics of a person’s tumor and/or a person’s overall genetic makeup. A personalized approach to cancer treatment helps spare people the side effects and cost of treatment that is not likely to be effective.
To date, three genetic mutations related to colorectal cancer are helping guide doctors in making treatment decisions.
KRAS MUTATIONS. Specific mutations in the KRAS gene are found in about four of 10 colorectal tumors. Testing for KRAS mutations is recommended for all people with metastatic disease, as studies have shown that tumors with this mutation do not respond to epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab and panitumumab. Because treatment depends on the results, testing must be done by approved methods at accredited facilities.
BRAF MUTATIONS. Mutations in the BRAF gene occurs less often than KRAS mutations (in about five to eight of every 100) and are found only in tumors that do not have KRAS mutations. Some studies have indicated that tumors with BRAF mutations are unlikely to respond to EGFR inhibitors, but more studies are needed to confirm this. Until the results of more studies are available, testing for the BRAF mutation is optional for people who have tumors that do not have KRAS mutations. Talk to your doctor about whether you should have this testing.
MISMATCH-REPAIR (MMR) GENE MUTATIONS (MICROSATELLITE INSTABILITY). Mutations in an MMR gene lead to a low level (deficiency) of MMR protein in the tumor. MMR deficiency is related to an abnormality known as microsatellite instability (MSI), and measuring MSI is another way to determine a low amount of MMR protein in the tumor. Tumors that have signs of MSI are known as MSI-high, which represents a low amount of MMR protein. MSI-stable means that the mutation is not present. A report of either an MSI-high tumor or a MMR deficient tumor is associated with a favorable outcome. Testing for MMR deficiency is recommended for people with colon cancer who are younger than 50 years at the time of diagnosis because MMR deficiency is strongly associated with HNPCC. Testing for MMR deficiency may also be useful for patients with stage II disease to help determine if adjuvant chemotherapy will be of benefit.
In addition to these tests, other genetic tests may be done on blood samples to see if you are at higher risk for serious side effects of 5-FU or irinotecan. These tests are usually done if side effects are severe after the initial dose. Talk to your doctor about whether these tests are appropriate for your situation.
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Radiation Therapy
Radiation therapy is the use of high-energy x-rays to kill cancer cells or keep them from growing. The type of radiation therapy used most often is external-beam radiation therapy, which is delivered from a machine outside of the body.
Radiation therapy is often used for patients with rectal cancers but is not typically used for colon cancer. Chemoradiation therapy is especially effective for rectal cancer and may be used as adjuvant therapy, to help reduce the risk of recurrence. Chemoradiation therapy is also particularly useful as neoadjuvant therapy, as many rectal cancers are more difficult to surgically remove than colon cancers. Neoadjuvant chemoradiation therapy helps to shrink the tumor, allowing for it to be removed more easily.
A radiation oncologist will oversee your radiation therapy. Before you begin actual treatment, your radiation oncologist will carefully plan your radiation therapy to calculate the appropriate dose and determine the optimum number of treatments. The number of radiation treatments will vary according to the type and stage of rectal cancer. Radiation therapy will not make you radioactive.
Supportive Care
Supportive (palliative) care is an essential part of your overall treatment plan. 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 ensure that people with cancer (or other diseases) receive care that prevents and/or relieves pain and other disease-related symptoms and that relieves the side effects of treatment.
You should receive palliative care throughout your course of treatment, no matter what stage of disease you have. Managing symptoms and side effects is important because if you feel better, you are more likely to complete your planned treatment, which offers a greater chance for a good outcome.
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.
Pain is the most feared cancer-related symptom, but no one with cancer should expect to endure pain. Several 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. Radiation therapy may be done to shrink such a tumor, which will alleviate both the blockage and the pain. In addition, a surgical procedure can be done to 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. You can learn more about these side effects here.
Other Types of Treatment
Chemotherapy, radiation therapy and surgery, as well as other types of procedures, are also options for treating metastatic tumors, and the procedures vary according to where the metastatic tumor is located. The most common site of colorectal cancer metastasis is the liver. The optimum treatment of liver metastasis is surgical removal of the metastatic tumor; however, this is not always possible. Chemotherapy may be given first to try to shrink the tumor enough to make it possible to remove. Chemotherapy drugs can also be delivered directly into the liver through its main blood vessel, the hepatic artery; this procedure is known as hepatic arterial infusion (HAI). Another option for treating liver metastasis is radiofrequency ablation (RFA), in which a probe is inserted into the liver tumor and a high frequency current is used to deliver heat through the probe; the heat destroys the cancer cells. Another option is to insert tiny radioactive beads through a catheter into the hepatic artery. With this procedure, known as selective internal radiation therapy (SIRT), the radioactive beads get trapped in the tiny blood vessels near tumors and give off radiation that destroys cancer cells. If your doctor suggests one of these procedures, it is highly recommended that you be evaluated by an experienced multidisciplinary team that includes surgeons, medical oncologists and radiation oncologists at a NCI-designated cancer center before you pursue any of these treatment options.
If colorectal cancer has spread to the lung, brain or bones, radiation therapy may be used to destroy the metastatic tumors. Your treatment team will talk to you about the options for treating metastases and the risk-benefit ratios of the procedures. Second opinions from experts can provide additional information.
Many people seek treatments other than the ones described here, with the hope of finding a cure. Nonconventional therapies have no scientific basis and are harmful when used instead of standard therapies that research has shown to be effective. In addition, many dietary or herbal supplements interfere with the action/effectiveness of some cancer treatments. Be sure to tell your doctor if you take any supplements — for your cancer or any other condition you have.
Making treatment decisions can be overwhelming because of the many factors to consider. Do not be afraid to ask your doctors or other members of your treatment team questions to help you better understand your options and the potential outcomes (Table 3). You should actively participate in the decision-making process and make your preferences known, especially preferences related to quality-of-life issues. Once a treatment plan is selected, it is most important that you follow it in order for it to be effective. Talk to your doctor about the possibility of participating in a clinical trial. A clinical trial offers the opportunity to receive the best available care for your particular cancer, with a chance to receive new treatment that has the potential to be even more effective than the current standard of care.
Importance of Clinical Trials
The advances in colorectal cancer over the past decades have been made through carefully monitored studies known as clinical trials. People who volunteer to take part in a clinical trial will receive the current standard treatment or a new treatment thought to be as good as or better than the standard treatment. Participants not only help themselves but can also feel good about helping to provide information that will help the future care of others, perhaps even their own family members.
Clinical trials are safe and are conducted under the care of physicians and other research professionals and sponsored by government agencies, such as the National Cancer Institute, by individual doctors and health care groups or by the pharmaceutical or biotechnology companies that developed the treatments.
To find a clinical trial that may be right for you, first ask your treatment team if they can suggest a clinical trial that might benefit you. In addition, a number of government and private groups have listings of clinical trials and information.
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Table 1. Types of Surgical Procedures for Colon or Rectal Cancer
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Types of Surgery |
Description |
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Colon Cancer |
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Polypectomy |
Removal of a polyp during colonoscopy. The instruments to remove the polyp are small and passed through the colonoscope, and no incision is made in the abdomen. |
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Colectomy |
Surgical removal of the section of colon containing the cancer. After the section is removed, the two ends of the colon are reattached with sutures (stitches) or staples. |
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Open |
The colectomy is done through a long incision made in the abdomen. Nearby lymph nodes are also removed; it is recommended that at least 12 lymph nodes be removed and evaluated. |
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Laparoscopic assisted |
A minimally invasive procedure in which the colectomy is done through several small incisions that are made in the abdomen. A laparoscope is inserted through one of the incisions, and special long surgical instruments, including one with a camera, allows the surgeon to see inside the abdomen. The amount of colon that can be removed is usually the same as the amount that can be removed in an open procedure. Recovery time is usually shorter because of the smaller incisions, and the outcome is similar to that after an open procedure. |
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Robotic assisted |
A minimally invasive procedure in which the colectomy is done with use of a computer and several robotic arms, each fitted with specialized instruments. (This technique may also be used for rectal cancers.) |
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Ostomy |
The creation of a stoma, or opening in the abdomen, and connecting the end of the colon or small intestine to the opening. An ostomy provides a new path for stool (body waste) to exit the body. The procedure is a colostomy when the colon is attached to the stoma and is an ileostomy when the end of the small intestine is attached to the stoma (to bypass all of the colon). |
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Rectal Cancer |
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Polypectomy |
Removal of a polyp during colonoscopy or sigmoidoscopy (see above). |
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Transanal excision |
Removal of the tumor and some normal tissue with use of instruments inserted through the anus. The procedure does not involve removal of lymph nodes. |
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Lower anterior resection |
Removal of the part of the rectum containing the cancer, as well as nearby lymph nodes. The colon is reconnected to the rectum so that bowel function can be maintained. |
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Total mesorectal excision |
Removal of the entire rectum (also known as proctectomy) and all of the lymph nodes near the rectum. The colon is connected to the anus in a procedure called a colo-anal anastomosis. |
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Abdominoperineal resection |
Removal of the rectum and the anal sphincter (the muscle that keeps the anus closed). Because the anus is removed, a permanent colostomy is needed. |
Table 2. Drugs Used to Treat Colon or Rectal Cancer
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Generic (Trade) Name |
Action of Drug |
Options for Use |
Notes |
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Capecitabine (Xeloda) |
Cytotoxic |
Adjuvant treatment of stage III colon cancer or treatment of stage IV colon cancer (alone or in combination with other drugs). |
Given orally |
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Fluorouracil, 5-FU (Adrucil)
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Cytotoxic
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The backbone of colorectal cancer treatment of all stages; usually given in combination with leucovorin (which enhances its effectiveness).
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Given intravenously, either as a bolus (given over a short period of time) or as an infusion given over a longer period of time.
If the side effects are severe after the initial dose, testing may be done to see if a genetic abnormality is the cause of the severe side effects.
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Irinotecan, CPT-11 (Camptosar) |
Cytotoxic |
Alone or in combination with other drugs, as treatment for metastatic or recurrent colon or rectal cancer. |
If the side effects are severe after the initial dose, testing may be done to see if a genetic abnormality is the cause of the severe side effects. |
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Leucovorin |
Chemosensitizer |
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Used in combination with 5-FU (to increase the effectiveness of 5-FU). |
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Levoleucovorin (Fusilev) |
Chemosensitizer |
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A chemical relative of leucovorin. Used as a substitute for leucovorin. |
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Oxaliplatin (Eloxatin) |
Cytotoxic |
In combination with other drugs, as adjuvant treatment or treatment of colon or rectal cancer that has progressed or recurred after previous chemotherapy. |
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Chemotherapy Regimens |
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CapeOX or XELOX |
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Capecitabine and oxaliplatin |
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FOLFOX |
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5-FU/leucovorin (infusional), oxaliplatin |
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FLOX |
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5-FU/leucovorin (bolus), oxaliplatin |
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FOLFIRI |
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5-FU/leucovorin, irinotecan |
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IROX |
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Irinotecan and oxaliplatin |
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Targeted Therapy Drugs |
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Bevacizumab (Avastin) |
VEGF* inhibitor |
In combination with chemotherapy drugs, as first-line or second-line treatment of metastatic colorectal cancer. |
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Cetuximab (Erbitux) |
EGFR* inhibitor |
Alone or in combination with irinotecan, as treatment for metastatic colorectal cancer that is refractory to irinotecan-based chemotherapy or for metastatic disease in people who cannot tolerate irinotecan-based chemotherapy. |
Testing for the KRAS mutation in the tumor is recommended, as tumors with this mutation are not likely to respond to the drug.
Testing for the BRAF mutation may be considered because of the increased likelihood that the tumor will not respond. (See Treatment of Colon and Rectal Cancer is Becoming Personalized sidebar above.) |
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Panitumumab (Vectibix) |
EGFR* inhibitor |
Treatment of metastatic colorectal cancer that has progressed during or after previous chemotherapy. |
Testing for the KRAS mutation is recommended, as tumors with this mutation are not likely to respond to the drug.
Testing for the BRAF mutation may be considered because of the increased likelihood that the tumor will not respond. (See Treatment of Colon and Rectal Cancer is Becoming Personalized sidebar above.) |
*VEGF = vascular endothelial growth factor; EGFR = epidermal growth factor receptor.
Table 3. Questions to Ask Your Doctors About Treatment
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Which type of surgical specialist should do my operation (surgical oncologist, general surgeon or colorectal surgeon)?
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How many operations for this kind of cancer do you perform each year? (He or she should perform a minimum of 12 operations per year.)
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Will a temporary or permanent ostomy be necessary?
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Is a laparoscopic-assisted technique an option for me?
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Will any of the other organs in the pelvis be affected by the operation?
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Is there a way to determine whether chemotherapy will be effective for me?
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What are the potential side effects of my planned treatment?
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Do I need chemotherapy and/or radiation therapy before the operation?
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What is the standard of care for my diagnosis? What do you recommend and why?
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Am I eligible for a clinical trial?
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If I have metastatic tumors, can they be treated? If so, what are the advantages and disadvantages of the treatment options? What is the risk of recurrence in my particular case?
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What is the prognosis for my particular cancer?
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Additional Sources of Information
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