Advances in Colon and Rectal (Large Bowel) Cancer Treatment - 2017 and 2018

Colon and rectal (large bowel) cancers are the third most common cancer type in women and men. Today, wider use of cancer screening allows 80% of patients to be diagnosed early before spreading through the body (metastasis ). Even in the last 5 years, deaths from colon cancer have fallen by approximately 10%.

-Related Topic:  What you need to know about colon and rectal cancer

Important developments in colon cancer in recent years include:

1. Physical activity and eating habits have demonstrated their importance in colon cancer too

A study reported at the American Psychosocial Oncology meeting emphasized the importance of eating habits and physical activity (exercise). Evaluating 411 gastrointestinal cancer patients' dietary habits and physical activity scores showed impaired quality of life in inactive patients. Those continuing alcohol use alongside a sedentary lifestyle had shorter survival.

Another study thus showed the importance of continuing physical activity and restricting alcohol after a cancer diagnosis (1).

2. Colonoscopy screening saves lives

Screening methods are extremely important for diagnosing cancer early. Since 2007, colonoscopy has been recommended for colorectal cancer screening in patients aged 50 and over.

Approximately 5000 colon cancer patients and 20 thousand controls were compared in a study evaluating the importance of colonoscopy screening, showing a 61% reduction in colorectal cancer deaths with colonoscopy (2).

3. Immunotherapy has demonstrated efficacy in colon cancer too

Microsatellite instability is genomic instability resulting from deficient DNA mismatch repair. Approximately 4% of colon cancer patients have this condition. In these patients, PD1-inhibiting immunotherapy drugs pembrolizumab (Keytruda) and nivolumab (Opdivo), acting through the immune system, proved effective in studies. With a benefit rate of approximately 50% and a survival contribution, pembrolizumab in May 2017 and then nivolumab in August 2017 received approval for metastatic colon cancer with high MSI or DNA repair deficiency from the FDA .

-Related Topic: What is microsatellite instability? What does DNA mismatch repair mean? (detailed)

Another study investigated combining two drugs developed against immune-suppressing checkpoints (this combination had demonstrated efficacy in malignant melanoma and kidney cancer). It combined the PD1 inhibitor nivolumab and the CTLA4 inhibitor ipilimumab.

The study enrolled patients previously treated with two or more chemotherapy lines: stage 4 colon cancer, 119 patients. The treatment benefit rate was 55%, and 1-year disease-free survival was 71%. Combined treatment offered more benefit without a difference in adverse effects (3). This combined regimen appears likely to find a place in treatment soon.

-Related Topic: What are immunotherapy drug side effects, and how are they treated?

4. Improving regorafenib tolerability is now easier

Regorafenib (brand name Stivarga) is one of the most important options in stage 4 colon cancer. Although its schedule is 160 mg for 3 weeks followed by 1 week without treatment, patients experienced problems due to side effects. A recent dose-adjustment study showed that starting at 80 mg and increasing weekly made regorafenib easier to use, reduced adverse effects and contributed to overall survival, meaning efficacy was not reduced (4).

5. In stage four large bowel cancer, targeted drugs will need to be selected according to right- or left-sided tumor location

During embryological development, the right and left bowel originate from different sites. This is one reason for their differing characteristics and genetic changes. Although the same chemotherapy drugs are used in metastatic colon cancer regardless of right-left location, use of targeted drugs may vary. A broad analysis evaluating many new clinical studies demonstrated the importance of tumor sidedness. In left-sided tumors that are genetically RAS mutation negative (nonmutant, wild-type), adding targeted drugs against the epithelial growth factor receptor (EGFR), [panitumumab (Vectibix) and cetuximab (Erbitux)], to chemotherapy contributed more to survival. In right-sided tumors, however, adding bevacizumab (Altuzan), a targeted drug against the vascular endothelial receptor, was more effective (5).

Personalized treatment now matters in colon cancer as in many other cancers. Assessing genetic changes, location and microsatellite status is very important when planning treatment.

6. In operated stage 3 colon cancer at low recurrence risk, 3 months of preventive chemotherapy is sufficient

Approximately 40% of newly diagnosed colon cancers are stage 3, primarily treated by surgically removing the cancerous area and neighboring lymph nodes. At this stage, cancer has invaded colon layers and metastasized to lymph nodes. The number of involved nodes (N) and depth in the colon layers (T1-4) divide stage-three disease into low- or high-recurrence-risk groups (low risk T1, T2, T3 and N1; high risk T4 and/or N2). Postoperative chemotherapy regimens (FOLFOX or CAPOX), combined for 6 months, are standard adjuvant (preventive) chemotherapy.

Oxaliplatin, the constant drug in these regimens, has a cumulative nervous-system effect, neuropathy, which is treatment's most unpleasant side effect. It impairs quality of life and occurs in nearly half of patients.

A study evaluating 12800 stage 3 colon cancers showed that 3 months of preventive chemotherapy was sufficient for low-risk patients. With 3 months of treatment, the likelihood of nerve damage decreased 3-fold.

Of stage 3 colon cancer patients, 60% are low risk. Identifying them and giving 3 months of preventive treatment will avoid unnecessary adverse effects.

- Video: Prof. Dr. Mustafa Özdoğan explains: Advances in colon cancer treatment and how long postoperative preventive adjuvant chemotherapy should last?