What`s new in colorectal cancer research and treatment?

Research is always going on in the area of colorectal cancer. Scientists are looking for causes and ways to prevent colorectal cancer as well as ways to improve treatments.

Genetics

Scientists are learning more about some of the inherited and acquired changes in DNA that cause cells of the colon and rectum to become cancerous. Recent discoveries of inherited genes that increase a person's risk of developing colorectal cancer are already being used in genetic tests to inform people most at risk.

Doctors have also found that some gene changes affect whether or not certain treatments may be effective. For example, colorectal cancers with changes in the KRAS or BRAF genes are not likely to be helped by certain targeted drugs such as cetuximab (Erbitux) or panitumumab (Vectibix). Doctors can now test for these gene changes, which may help spare some people from getting unnecessary treatments.

People whose colon or rectal cancers show DNA mismatch repair (MMR) defects tend to survive longer after surgery than those who cancers do not. However, these cancers are less likely to be helped by chemotherapy combinations that include 5-fluorouracil (5-FU) given as adjuvant treatment after surgery. Therefore, studies are testing the effectiveness of chemotherapy that does not include 5-FU for patients with stage II or III colorectal cancers that have this molecular feature.

A new test has been developed that looks at the activity of 18 different genes in the cancer. It can be used to help predict which patients with stage II colon cancer may benefit from adjuvant chemo.

Advances in understanding how gene changes cause colorectal cancer may also eventually lead to new drugs and gene therapies to correct these gene problems. Early phases of gene therapy trials are already in progress.

Chemoprevention

Chemoprevention uses natural or man-made chemicals to lower a person's risk of developing cancer. Researchers are testing whether certain supplements, minerals (such as calcium), and vitamins (such as folic acid or vitamin D) can lower colorectal cancer risk.

Some studies have found that people who take multi-vitamins containing folic acid (also known as folate), vitamin D supplements, or calcium (through either diet or supplements) may have a lower colorectal cancer risk than people who do not. Research to clarify the possible benefits of these and other substances, such as selenium and curcumin, is now under way.

Taking aspirin or another nonsteroidal anti-inflammatory drug (NSAID) is associated with a lower risk of colorectal cancer, but these drugs can cause stomach ulcers and other side effects. This is why taking NSAIDs specifically for this purpose is not recommended for people at average colorectal cancer risk.

NSAIDs, such as sulindac and celecoxib (Celebrex®), have been shown to reduce formation of adenomatous polyps in people with familial adenomatous polyposis (FAP). The FDA has approved celecoxib for reducing polyp formation in people with FAP. However, celecoxib may have side effects such as a potential increased risk of heart disease. Consult your doctor before beginning regular use of aspirin or another NSAID.

Many people take drugs known as statins to lower their cholesterol levels. These drugs may also help lower the risk of polyps and colorectal cancer. A study currently going on is looking to see if giving rosuvastatin (Crestor®) to people who had a polyp or early colon cancer will lower the risk of a new colon cancer or polyp or lower the risk of the cancer coming back.

Earlier detection

Colorectal cancer is much easier to treat effectively if it is found at a very early stage. Studies continue to look at the effectiveness of current colorectal cancer screening methods and assess new ways to tell the public about the importance of being screened.

Only about half of Americans age 50 or older have had any colorectal cancer screening at all. If everyone were tested as recommended, thousands of lives could be saved each year. The American Cancer Society and other public health organizations are working to increase awareness of colorectal cancer screening among the general public and health care professionals.

Meanwhile, new imaging and lab tests are also being developed and tested. Newer, more accurate ways to look for changes in the stool that might indicate colorectal cancer have been developed. These include tests that are better able to detect blood in the stool (fecal immunochemical tests) and test that can detect changes in the DNA of cells in the stool.

CT colonography (also known as virtual colonoscopy) is a special type of CT scan that can find many colorectal polyps and cancers early. A recent study found that it could be helpful in screening even without the patient having to drink large amounts of liquid laxative first.

These tests are described in more detail in the section, “Can colorectal polyps and cancer be found early?”

Treatment

Newer surgery techniques

Surgeons are continuing to improve their techniques for operating on colorectal cancers. They now have a better understanding of what makes colorectal surgery more likely to be successful, such as making sure enough lymph nodes are removed during the operation.

Laparoscopic surgery is done through several small incisions in the abdomen instead of one large one, and it's becoming more widely used for some colon cancers. This approach usually allows patients to recover faster, with less pain after the operation.

Laparoscopic surgery is also being studied for treating some rectal cancers, but more research is needed to see if it as effective as standard surgery. With robotic surgery, a surgeon sits at a control panel and operates very precise robotic arms to perform the surgery. This type of surgery is also being studied.

Chemotherapy

Many clinical trials are testing new chemotherapy drugs or drugs that are already used against other cancers (such as cisplatin or gemcitabine). Other studies are looking at new ways to combine drugs already known to be active against colorectal cancer, such as irinotecan and oxaliplatin, to improve their effectiveness. Still other studies are testing the best ways to combine chemotherapy with radiation therapy, targeted therapies, and/or immunotherapy.

Targeted therapy

Several targeted therapies are already used to treat colorectal cancer, including bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix). Doctors continue to study the best way to give these drugs to make them more effective.

Targeted therapies are currently used to treat advanced cancers, but newer studies are trying to determine if using them with chemotherapy in earlier stage cancers as part of adjuvant therapy may further reduce the risk of recurrence.

Researchers are also studying new targeted therapy drugs to give more options to people with colorectal cancer. One of these, ziv-aflibercept (Zaltrap®), was recently approved by the FDA to treat advanced colon cancer. Like bevacizumab, it is a protein that binds to vascular endothelial growth factor (VEGF), which can stop tumors from making new blood vessels. Ziv-aflibercept is given as an infusion into a vein (IV) every 2 weeks. In one study, adding this drug to the chemotherapy combination FOLFIRI (5-FU, leucovorin, and irinotecan) helped patients with advanced colorectal cancer who had already been treated with FOLFOX (5-FU, leucovorin, and oxaliplatin) live about 6 weeks longer than giving FOLFIRI alone.

Common side effects include high blood pressure, tiredness, bleeding, low white blood cell counts, low platelet counts, headaches, mouth sores, loss of appetite, diarrhea, and abnormal lab tests of liver and kidney function. Rare but serious side effects can occur, such as blood clots, severe bleeding, holes forming in the colon (called perforations), and slow wound healing.

Regorafenib (Stivarga®) is another new targeted drug for advanced colorectal cancer. It is a type of targeted therapy known as a kinase inhibitor. Kinases are proteins on or near the surface of a cell that transmit important signals to the cell's control center. Regorafenib blocks several kinase proteins that either prompt tumor cells to grow or help form new blood vessels to feed the tumor. Blocking these proteins can help stop the growth of cancer cells.

This drug was studied in patients after treatment with most of the drugs approved to treat colorectal cancer: 5-FU, irinotecan, oxaliplatin, bevacizumab, and, in some cases a drug that targets EGFR (cetuximab or panitumumab). In one study, regorafenib helped these patients live on average about 6 weeks longer.

This drug is given in pill form. Common side effects include fatigue, decreased appetite, hand-foot syndrome (redness and irritation of the hands and feet), diarrhea, sores in the mouth and throat, weight loss, voice change, infections, and high blood pressure. Some serious side effects that can occur include liver damage, severe bleeding, and perforations in the stomach or intestines.

Immunotherapy

Researchers are studying several vaccines to try to treat colorectal cancer or prevent it from coming back after treatment. Unlike vaccines that prevent infectious diseases, these vaccines are meant to boost the patient's immune reaction to fight colorectal cancer more effectively.

Many types of vaccines are being studied. For example, some vaccines involve removing some of the patient's own immune system cells (called dendritic cells) from the blood, exposing them in the lab to a substance that will make them attack cancer cells, and then putting them back into the patient's body. At this time, these types of vaccines are only available in clinical trials.