Chemotherapy for colorectal cancer

Chemotherapy (chemo) is treatment with anti-cancer drugs.

How is chemotherapy given?

Chemotherapy can be given in different ways.

Systemic chemotherapy: Systemic chemotherapy uses drugs that are injected into a vein or given by mouth. These drugs enter the bloodstream and reach all areas of the body. This treatment is useful for cancers that have metastasized (spread) beyond the organ they started in.

Regional chemotherapy: In regional chemotherapy, drugs are injected directly into an artery leading to a part of the body containing a tumor. This approach concentrates the dose of chemotherapy reaching the cancer cells. It reduces side effects by limiting the amount reaching the rest of the body.

Hepatic artery infusion, where chemotherapy is given directly into the hepatic artery, is an example of regional chemotherapy sometimes used for colon cancer that has spread to the liver.

When is chemotherapy used?

Chemotherapy may be used at different times during the treatment of colon or rectal cancers.

Adjuvant chemotherapy: Chemotherapy used after surgery to remove the cancer is known as adjuvant chemotherapy. It can help keep the cancer from coming back later and has been shown to help people with stage II and stage III colon cancer and rectal cancer live longer. It is given after all visible cancer has been removed to lower the chance that it will come back. It works by killing the small number of cancer cells that may have been left behind at surgery because they were too small to see. Adjuvant chemo is also aimed at killing cancer cells that may have escaped from the main tumor and settled in other parts of the body (but are too small to see on imaging tests).

Neoadjuvant chemotherapy: For some cancers, chemotherapy is given (along with radiation) before surgery to try to shrink the cancer and make surgery easier. This is known as neoadjuvant treatment and is often used in treating rectal cancer.

Chemotherapy for advanced cancers: Chemotherapy can also be used to help shrink tumors and relieve symptoms for cancers that have spread to other organs, such as the liver. Although it is not likely to cure the cancer, it often helps people live longer.

Drugs used to treat colorectal cancer

Several drugs can be used to treat colorectal cancer. Often, 2 or more of these drugs are combined to try to make them more effective.

Chemo drugs are very strong medicines that can also affect some healthy cells in the body. Doctors give the drugs in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Chemotherapy cycles generally last about 2 to 4 weeks, and people usually get at least several cycles of treatment.

5-Fluorouracil (5-FU) and leucovorin: 5-FU has been in use for several decades, and it is part of most chemotherapy regimens for colorectal cancer. It is usually given together with a drug called leucovorin (or folinic acid), which makes it work better.

This drug may be given as an infusion into a vein over 2 hours, or (more commonly) as a quick injection followed by continuous infusion over 1 or 2 days. For continuous infusions, the patient wears a small battery-operated pump that infuses 5-FU into an intravenous (IV) catheter.

For most chemotherapy regimens, treatment with 5-FU is repeated every 2 weeks, over a period of 6 months to a year.

Capecitabine (Xeloda®): This is a chemotherapy drug in pill form. Once in the body, it is changed to 5-FU when it gets to the tumor site. This drug seems to be about as effective as giving continuous intravenous 5-FU with leucovorin.

Capecitabine is usually taken twice a day for 2 weeks, followed by a week off.

Irinotecan (Camptosar®): This drug is often combined with 5-FU and leucovorin (known as the FOLFIRI regimen) to treat advanced colorectal cancer. In some cases it may be tried by itself as a second-line treatment if other chemotherapy drugs are no longer effective. It is given as an IV infusion over 30 minutes to 2 hours.

One problem with irinotecan is that some people's bodies aren't able to break down the drug, so it stays in the body and causes severe side effects. This is due to an inherited gene variation that can be tested for. The simplest test is to measure the blood level of bilirubin, a substance made in the liver. If it is slightly elevated, this can be a sign of the gene variation that makes people sensitive to irinotecan. So far, most doctors aren't routinely testing for the gene variant itself.

The major possible side effects of irinotecan are severe diarrhea and low blood counts, although other effects such as nausea are possible as well. Your doctor may not use irinotecan if you are elderly or have serious health problems. In rare cases, severe side effects can be life-threatening.

Oxaliplatin (Eloxatin®): This drug is usually combined with 5-FU and leucovorin (known as the FOLFOX regimen) or with capecitabine (known as the CapeOX regimen) to treat colorectal cancer. Oxaliplatin is given as an IV infusion over 2 hours, usually once every 2 or 3 weeks.

Drugs and drug combinations often used to treat colon and rectal cancer

Common drug combinations used for adjuvant treatment include:

• FOLFOX: 5-FU, leucovorin, and oxaliplatin (this is most often used)
• 5-FU and leucovorin (this may be used if the patient has too many side effects with FOLFOX)

For treatment of cancer that has spread, there are many options, including

• FOLFOX: 5-FU, leucovorin, and oxaliplatin
• FOLFIRI: 5-FU, leucovorin, and irinotecan
• FOLFOXIRI (leucovorin, 5-FU, oxaliplatin, and irinotecan)
• CapeOx: Capecitabine and oxaliplatin
• 5-FU and leucovorin
• Capecitabine
• Irinotecan

Sometimes, these chemo drugs are given along with a targeted therapy drug (discussed in the next section)

For rectal cancer, chemo with 5-FU or capecitabine combined with radiation may be given before surgery (neoadjuvant treatment).

Side effects of chemotherapy

Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken. General side effects of chemotherapy drugs can include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Increased chance of infections (due to low white blood cell counts)
• Easy bruising or bleeding (due to low blood platelet counts)
• Fatigue (due to low red blood cell counts)

Along with these, some side effects are specific to certain medicines, for example:.

Hand-foot syndrome can occur during treatment with capecitabine or 5-FU (when given as an infusion). This starts out as redness in the hands and feet, which can then progress to pain and sensitivity in the palms and soles. If it worsens, blistering or skin peeling can occur, sometimes leading to open, painful sores. It is important to tell your doctor right away about any early symptoms, such as redness or sensitivity, so that steps can be taken to keep things from getting worse.

Neuropathy (painful nerve damage) is a common side effect of oxaliplatin. Symptoms include numbness, tingling, and even pain in the hands and feet. It can also cause patients to have intense sensitivity to hot and cold in the throat and esophagus (the tube connecting the throat to the stomach). This can cause problems (such as pain) swallowing liquids. If you will be getting oxaliplatin, talk with your doctor about side effects beforehand, and let him or her know right away if you develop numbness and tingling or other side effects.

Diarrhea is a common side effect with many of these drugs, but can be particularly bad with irinotecan. It needs to be treated right away - at the first loose stool - to prevent severe dehydration. This often means taking drugs like loperamide (Imodium®) many times. If you are on a chemo drug that is likely to cause diarrhea, your doctor will give you instructions on what drugs to take and how often to take them to control this symptom.

Most side effects are short-term and tend to go away after treatment is finished. Some, such as hand and foot numbness, may persist for a long-time. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Do not hesitate to discuss any questions about side effects with the cancer care team.

You should report any side effects or changes you notice while getting chemotherapy to your medical team so that they can be treated promptly. In some cases, the doses of the chemotherapy drugs may need to be reduced or treatment may need to be delayed or stopped to prevent the effects from getting worse.

Elderly people seem to be able to tolerate chemotherapy for colorectal cancer fairly well. There is no reason to withhold treatment in otherwise healthy people simply because of age.

For more general information about chemotherapy, please see our document, Understanding Chemotherapy: A Guide for Patients and Families.