Reducing the Burden of Polyps in FAP Patients

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Patients with familial adenomatous polyposis (FAP) are at a markedly increased risk for colorectal polyps and cancer. In fact, the risk of developing CRC is nearly 100% if FAP goes untreated and unmanaged. Therefore, there are multiple, critical management issues during the entire course of those affected with FAP. According to Evelyn Keener, FAP patient,
Living with FAP has not been easy. Over the past 43 years my screening has been 1-2 times a year and each time polyps are being found in my stomach, esophagus and small intestine. I would love if there was a treatment that could reduce the number of screenings and ultimately reduce polyps and precancerous cells often found. For me, I know having such drastic surgery at the age of eight left me unable to have children. It is something that haunts me daily.
Interestingly, there is substantial ongoing research looking into whether or not the growth of polyps can be reversed, in hopes of reducing the need for such intensive management and ultimately, preventing colorectal cancer.

What is FAP?

FAP is the second most common form of hereditary colorectal cancer (CRC). It occurs in 1 in 10,000 people and is detected by the growth of hundreds to thousands of adenomas (one type of colonic polyp) in the colon. The polyps often begin at a very early age. If not detected, CRC will likely develop in nearly all patients with FAP. There is also a slightly higher risk for other cancers, including stomach, duodenal, thyroid and brain cancers, desmoid tumors and bony growths, in addition to hepatoblastoma in infants (a specific liver tumor). It’s estimated that a quarter of FAP cases are de novo, meaning the individual has no family history of FAP or colonic polyposis. The diagnosis of FAP is made through genetic testing. FAP is caused by mutations in the adenomatous polyposis coli (APC) gene, which belongs to a family of genes called tumor suppressors. Tumor suppressors play an important role in preventing cancer by making sure cells grow and divide properly – not uncontrollably. Currently, the standard of care for APC mutation carriers (which include FAP patients), according to the American Society of Clinical Oncology, includes the following:
  • Sigmoidoscopy or colonoscopy every 1 to 2 years, starting at age 10-11
  • Colonoscopy every year once polyps are found until there are plans for the surgical removal of the colon (this surgery is called a colectomy).
  • Frequent sigmoidoscopy after colon surgery (depending on the surgery performed).
  • Upper endoscopy starting at age 25-30, or once colorectal polyps are found, whichever occurs first
    • every 6 to 12 months if some rectal tissue remains
    • every 1 to 4 years if all rectal tissue has been removed and there is a small intestinal pouch
  • Yearly ultrasound of the thyroid starting at age 25-30
  • Computed tomography scan or MRI if a person has a personal or family history of desmoid tumors
Part of treatment may include prophylactic colectomy - which is a surgery to remove part or all of the colon in order to prevent the recurrence of disease.

Research to reduce the burden of polyps in FAP patients

Recently, there has be research looking into whether or not the growth of polyps can be reversed, in hopes of reducing the need for such intensive management and diagnoses of cancer. One recent study published in May 2018 in the Journal of Medical Oncology (JAMA) discusses the use of chemotherapy for prevention of colorectal polyps in FAP patients. The goal? To reduce the need for additional endoscopic treatment and surgery.
According to the paper, “In this secondary analysis of the FAP Erlotinib-Sulindac Trial, a phase 2 randomized placebo-controlled trial of sulindac and erlotinib in 82 patients with FAP, treatment with sulindac and erlotinib was associated with a 69% reduction in colorectal polyp burden in patients with FAP.”

What are sulindac and erlotinib?

Sulindac is a non-steroidal anti-inflammatory drug similar to aspirin and ibuprofin. These drugs are all  cyclooxygenase (COX) inhibitors. Previous studies have shown that COX inhibitors can slow or stop the growth of colorectal adenomatous polyps in patients with FAP. Erlotinib is an epidermal growth factor receptor-inhibitor. (Learn more about EGFR-inhibitor drugs in our Skin Toxicity Mini Magazine.)

What did the study entail? What were the results and side effects?

This study was designed to look at the effects of sulindac and erlotinib on gastroduodenal adenomas. It is a secondary analysis of the study, including 82 randomized patients. Of the group, twenty-two had an with intact colon, forty-four had a total colectomy with an ileoanal anastomosis (J-pouch), and sixteen had a total abdominal colectomy with an ileorectal anastomosis (IRA). Forty-six of the patients were randomized to daily sulindac and erlotinib, and the rest received a placebo. After six months of the study, “results showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after six months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum.” Results of the study showed a median decrease of 27 polyps from start of the study in the sulindac and erlotinib group from the start of the study. The placebo group only showed a median of 2 polyp decrease. The most common side effect was skin rash, however some patients developed oral mucositis, diarrhea, and nausea.

[button] For information on how to manage skin rash, visit our resources on Skin Toxicity! [/button]

What does this mean for people with FAP?

While the results of this study are promising, it is still not known if long-term treatment with these medications can delay or replace the need for the therapies and treatments listed above. It is not certain if the use of sulindac and erlotinib can inhibit developing cancer. It is clear though, that the combination could suppress polyps in many FAP patients, and it is exciting to see strides in FAP research. According to Evelyn,

FAP is so important to promote because although it is precancerous, the effects and dangers are just as significant in the cancer research battle we face each day. We suffer, we struggle, we have life altering decisions to make and death is something we fight against daily. We deserve a face and a treatment that works to help reduce the risk and maybe even eliminate  the need for surgery.

Although a colectomy is a better alternative to getting cancer I’m sure most people with FAP would like a less invasive and life changing option as well. We have to find a way to make this disease more manageable - with more research and treatment options - maybe we can make things better for the next generation. Just writing this brings back 42 years of memories that bring tears to my eyes. Let’s make a difference. Let’s keep up the fight.

Stay up to date on screening!

It’s important for all FAP patients to stay up to date on screening and surveillance. For specific recommendations, visit the American College of Gastroenterology http://gi.org/wp-content/uploads/2015/02/ACG_Guideline_Hereditary-Gastrointestinal-Cancer-Syndromes_February_2015.pdf For more information about FAP, including the genes involved, testing and surveillance, and additional surveillance, download the Fight CRC Genetics Mini Magazine. Donate Research References Giardiello  FM, Hamilton  SR, Krush AJ,  et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis.  N Engl J Med. 1993;328(18):1313-1316. Jasperson, Tuohy, Neklason, Burt. Hereditary and Familial Colon Cancer. Gastroenterology. June 2010; 138(6): 2044-2058t