Why Do the New Drugs Fail in Adjuvant Chemotherapy?

Some of the most surprising data presented at the GI Symposium in January 2011 in San Francisco was the negative result of the European trial called AVANT.

Dr. Lenz Photo

Dr. HJ Lenz

In that clinical trial patients who underwent a curative resection for colon cancer received either FOLFOX or FOLFOX with Avastin® (bevacizumab) treatment after their surgery. Chemotherapy was given over 6 months, but patients who were randomly selected for Avastin received 6 months with chemotherapy and additional  6 months alone after chemotherapy ended for a total of 12 months of Avastin.

In our annual ASCO meeting in Chicago in 2009, we heard the results of an American trial (C-08) showing no benefit in patients who received Avastin in this setting, however there an interesting finding that during the 12 months Avastin was given there was a potential benefit. The European AVANT trial showed very similar results. Avastin did not improve outcome in patients who underwent a successful surgery for their colon cancer. There was again a hint of benefit during the time of Avastin therapy.

What does this all mean? After the negative data with Erbitux® and now with Avastin, we are coming to understand that drugs which work for metastatic disease may not have the same effect in patients who have only microscopic disease. The way these drugs work may be completely different if there only cells left or a tumor which has different infrastructure such as its own blood vessels and has overcome the defense of the immune system.

We need to get smarter and develop specific therapies for these patients and find out why the tumors in these patients come back. What makes colon cancer cells survive in some patients? How do some patients kill left over colon cancer cells?

We are back to the drawing board going beyond the pathology report to make treatment decisions but needing to understand the genetic make up of these cancers.


  1. patti B says

    my husband had surgery on march 7, 2012 He had no symptoms until two months before . Pains in the belly and lots of gas noses? miss diagnosed as bactiera, c-diff then through a scope they say the large mass in his right colon and cecal valve too those out but said it had went into 15 out of 20 lymph nodes called it stage 4 and now say maybe stage 3c with it not in ct scan done afterwards of chest, pelvic & liver not iin those areas? going to start chemo monday 4/15 do you think he needs avasin? told there are alot of bad side effects?

    • Kate Murphy says

      Before deciding on chemotherapy, you need to know for sure what stage the cancer is.

      If there is no evidence that cancer has spread to liver, lungs, or other places beyond the colon and the nearby lymph nodes, it is most likely stage 3C. Spread into those lymph nodes makes it stage 3, spread into 15 nodes makes it stage 3C.

      Avastin doesn’t benefit patients with stage 3 colon cancer. Two studies show that after three years, there is no difference in the percentage of people who were alive and cancer-free whether or not Avastin was added to chemotherapy. AVANT trial. C-08 trial.

      Adding Avastin to chemotherapy for Stage 4 colorectal cancer does improve survival time, so it is critical to get the right staging here. If there is any question, you should get a second opinion.

  2. SR says

    After reading the blog and responses, I was hoping that someone can tell me how their stage of cancer was diagnosed before surgery. My father has recently been diagnosed with rectum cancer based on byopsy results of his tumor found during colonoscopy. However the GI surgeon suggested that nothing can be told before he is operated. Is that true ?
    What is the general recovery period after the surgery ? My father is 71 and we all very worried..

    • Kate Murphy says

      Rectal cancer is gets a preliminary clinical stage before surgery and a pathology stage after any presurgical treatment and surgery.

      Besides the biopsy during his colonoscopy, initial tests for rectal cancer include:

      • either a rectal ultrasound or MRI to determine how deep into the wall of the rectum or surrounding tissue the tumor goes
      • the ultrasound or MRI will also indicate if there are enlarged lymph nodes nearby that might contain cancer cells.
      • the colonoscopy and, perhaps a rectal exam, will tell doctors how far up the rectum the tumor is, which helps in surgical planning.
      • a CT scan of the chest, abdomen, and pelvis looks for signs that cancer may have spread beyond the rectum and its nearby tissues.

      This determines the clinical stage and helps determine the treatment plan.

      Depending on how far the tumor extends and whether there is spread to nearby lymph nodes, radiation with chemotherapy may be given before surgery to shrink the tumor and improve the chances that the cancer won’t return locally.

      After surgery the pathologist measures the tumor and looks for cancer cells in the lymph nodes. This determines the pathological stage.

      Read more details about staging here.

      Your Dad’s surgeon should be able to tell you the clinical stage after initial testing, but the surgeon is right that the pathological stage needs to wait for surgery.

      If you have not yet talked to a colorectal surgeon, it is really important to do so. Rectal cancer is complicated surgery and requires special training and good experience. You can locate members of the American Society of Colon and Rectal Surgeons near you on the ASCRS site.

      Recovery time after surgery depends a lot on the type of surgery done and the individual patient, but usually is somewhere between 4 and 6 weeks. Some surgeons are now doing rectal surgery laparoscopically with shorter recovery times.

      If you or your Dad have more questions, you can call the Fight Colorectal Cancer Answer Line, and Tavia or Kim can give you more specific answers.

      Call the Answer Line at 1-877-427-2111
      9:00 AM – 5:00 PM Eastern time, Monday – Friday

  3. JW says

    Kate, therein lies the problem. The number one symptom of colon is no symptoms. My husband was diagnosed at age 48 with stage IV cancer. He started having problems evacuating his bowel completely 3 weeks before he had emergency surgery for a bowel blockage. And we all know that he didn’t go to stage IV in 3 weeks.

    So to simply say that knowing the symptoms will get it diagnosed early isn’t going to work, when many times there aren’t any symptoms.

  4. JW says

    We need to get smarter and figure out what causes some people to develop colon cancer and while another person with the exact same lifestyle doesn’t. We call colonoscopies a prevention method, when really they’re not, they’re a detection method. Prevention is stopping something, in this case polyps, from ever occuring in the first place. And if you’re under the age of 50 with no family history, then your just plain out of luck. Your colon cancer will probably not be detected until you are at the Stage IV level.

    • Kate Murphy says

      While colonoscopies don’t prevent polyps, they do prevent cancer — and that is why they are key.

      As for under 50’s –knowing the symptoms of colon and rectal cancer can get cancer diagnosed at an early stage. My own stage III cancer was discovered and successfully treated when I was 40.

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