Colon Cancer: Declining Mortality Rates

Colorectal cancer, also called colon cancer, is the second leading cause of cancer-related deaths in the United States of the cancers affecting both men and women.¹ Colon cancer, when detected early, is highly treatable. Proper screening can discover precancerous polyps or early stage colon cancer and result in curative treatment.

EPIDEMIOLOGY

The American Cancer Society (ACS) estimates that in 2017 more than 95,000 people in the United States will be diagnosed and more than 50,000 deaths will result from colon cancer.² Ninety percent of cases occur in individuals older than 50 years. Other predisposing risk factors include inflammatory bowel disease, a personal or family history of colon cancer or polyps, history of Streptococcus bovis bacteremia, type 2 diabetes, use of uterosigmoidoscopy, or a hereditary syndrome.³ Lifestyle factors such as inactivity, a low-fiber or high-fat diet, a diet low in fruits and vegetables, being overweight or obese, or alcohol or tobacco use also can contribute to the risk of developing colon cancer.³

Despite the prevalence of colon cancer, overall mortality rates have been declining. Possible contributing factors have been hypothesized to be a decrease in overall incidence, better screening tools resulting in earlier detection, more effective available treatments, changes in dietary habits, and nonsteroidal anti-inflammatory drug use and use of other medications that affect the gut flora.⁴

SCREENING

Randomized, controlled trials have shown lower mortality in patients who undergo screening than in those who do not, with the rationale that early detection of localized, superficial cancers will increase the surgical cure rate.

According to guidelines set by the ACS, the average-risk patient should get screened for colorectal cancer starting at age 50. A variety of screening methods are available and recommended with corresponding advantages and disadvantages. Screening methods include flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, double contrast barium enema every 5 years, computed tomography colonography every 5 years, annual fecal occult blood test, or annual fecal immunochemical test.⁵ Patients at a higher risk (ie, those with a personal or family history of colon cancer or precancerous polyps, a personal history of inflammatory bowel disease, or a hereditary syndrome contributing to colon cancer) may need to begin screening at an earlier age or be screened more often.^3,5

TREATMENT

The mainstays of colon cancer treatment are surgery, radiation, and chemotherapy. Treatments vary based on tumor staging and individual patient characteristics.^3,6

For localized colon cancer in stages I-III, surgical resection is the primary method of treatment. The extent of the cancer in further stages determines the strategy. Radiation therapy may be added before or after surgery in advanced or metastatic disease to increase a tumor’s resectability or to reduce the probability of reoccurrence.⁶

Adjuvant chemotherapy is standard following surgery in stage III cancer but controversial in stage II.^6,7 For stage II, surgery alone is the only curative treatment, but about 20% to 30% of patients have tumor recurrence. Chemotherapy may be recommended in patients with higher risk of recurrence; however, the American Society of Clinical Oncology (ASCO) does not advocate routine use of adjuvant chemotherapy in patients with stage II disease and recommends that they participate in clinical trials.⁷

The most widely used and studied chemotherapy agent for colon cancer is 5-fluorouracil (5-FU).^3,6 5-FU is frequently usedin combination with leucovorin. Other agents include oxaliplatin, irinotecan, and capecitabine. FOLFOX (5-FU, leucovorin, and oxaliplatin) and CapeOx (capecitabine and oxaliplatin) are among the most frequently used regimens, but some patients may get different combinations depending on their age and health needs. The addition of oxaliplatin to 5-FU has shown significant disease-free survival at 3 years in patients with stage III colon cancer.⁸ In the XACT trial, capecitabine was shown to be noninferior to 5-FU/leucovorin as adjuvant therapy in patients with stage III colon cancer.⁹

In patients with metastatic disease, surgery is unlikely to eradicate cancer; however, depending on the extent and location of the metastases, surgery may prolong survival and result in a cure. Patients with stage IV cancer often receive adjuvant chemotherapy or other targeted treatment.

In September 2015, the FDA approved the nucleoside-analogue oral chemotherapy drug tipiracil/trifluridine (Lonsurf) based on the results of the RECOURSE trial, which showed increased median overall survival in metastatic disease compared with placebo.¹⁰

Biologic agents have also been studied, and several have been approved for patients with metastatic disease. Therapy targeting either vascular endothelial growth factor or epidermal growth factor includes bevacizumab, ramucirumab, ziv-aflibercept, cetuximab, and panitumumab. The kinase inhibitor regorafenib has been approved for patients with previously treated metastatic colon cancer.⁶

Chemotherapy toxicities can be treatment limiting and can differ depending on the dose, route, and schedule of the therapy. Leukopenia and hand-foot syndrome are affiliated with 5-FU. Hand-foot syndrome is also associated with capecitabine, and neuropathy has been associated with oxaliplatin. Diarrhea can occur with many agents, with irinotecan being the most severe. Other toxicities include stomatitis, nausea and vomiting, allergic or sensitivity reactions, hair loss, appetite loss, fatigue, and neutropenia.

PREVENTION

Colon cancer prevention should focus on lifestyle modifications, regular screening, and pharmacologic prevention.⁶ An analysis of several large adjuvant trials showed that 85% of colon cancer recurrence occurs within the first 3 years after resection of the primary tumor, with 95% of the recurrences happening by year ⁵. Because of this, ASCO recommends regular screening for patients with resected colon cancer for at least 5 years after diagnosis.

Some pharmacologic agents have been researched for colon cancer prevention. The selective cyclooxygenase-2 inhibitor, celecoxib, has been tested in patients with familial adenomatous polyps and was successful in decreasing the size and number of polyps on subsequent colonoscopies. Further research is needed to determine whether this translates to reduced cancerincidence. The cardiac toxicity of these drugs should also be weighed against the benefits.

Aspirin use has been proven effective in primary prevention (doses more than 300 mg daily for 5 years) or secondary prevention (doses 81-325 mg daily). A study in 2013 showed that lowdose aspirin (100 mg) taken every other day decreases the risk of colorectal cancer in women aged 45 after 10 years by 20%.¹¹

PHARMACIST’S ROLE

Pharmacists can positively influence patients with colon cancer in all practice settings and can be instrumental in screening, education, treatment, and adverse effect management. If colon cancer is caught at an early stage, affected patients have up to a 90% 5-year survival rate. According to the National Health Interview Survey, in 2015, 62.9% of adult Americans between 50 and 75 years of age had undergone colon cancer screening. Pharmacists can help identify patients who need to be screened by age and risk.¹²

Pharmacists also provide education and counseling to patients. Screening procedures can be scary and complicated for patients, and pharmacists can counsel patients on the importance of screening, how to take bowel preparations, and what to expect from procedures. Modifiable lifestyle factors that may contribute to colon cancer risk or recurrence risk, including physical activity, waist circumference, smoking, alcohol consumption, and diet, should also be part of patient education.

Additionally, pharmacists can be influential in selecting chemotherapy regimens and providing supportive care to patients with cancer. By optimizing outcomes of symptom management, educating about therapy and disease, and providing drug therapy, pharmacists can contribute to the overall care of patients with colon cancer.

Joanna Lewis graduated from the Medical University of South Carolina in 2007. Since then, she has held a variety of pharmacy practice roles, most recently a leadership position in the Department of Pharmacy at Duke University Hospital. Some of her responsibilities included medication safety, quality improvement, oversight of the financial charge captureprocess, and coordinating the implementation of a new technology system. She is passionate about precepting and mentoring new practitioners, as well as making the practice ofpharmacy better.

References

• Centers for Disease Control and Prevention. Colorectal (Colon) Cancer. https://www.cdc.gov/cancer/colorectal/. Last updated March 23, 2017. Accessed April 26, 2017.
• American Cancer Society. Colorectal Cancer Facts & Figures 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2017-2019.pdf. Accessed April 30, 2017.
• Mayer, RJ. Gastrointestinal Cancer. In: Longo DL, Fauci AS, Kasper, DL et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw Hill Medical; 2012.
• Welch, HG and Robertson, DJ. Colorectal Cancer on the Decline - Why Screening Can't Explain it All. N Engl J Med. 2016; 374: 1605-1607.
• American Cancer Society. Colorectal Cancer Early Detection Screening and Surveillance Guidelines (2008). https://www.cancer.org/health-care-professionals/american-cancer-society-prevention-early-detection-guidelines/colorectal-cancer-screening-guidelines.html. Accessed April 26, 2017.
• Dragovich T, and Tsikitis V. Colon Cancer Treatment and Management. Medscape: http://emedicine.medscape.com/article/277496-treatment#d1. Last updated May 1, 2017. Accessed May 1, 2017.
• Benson AB, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology. Recommendations on Adjuvant Chemotherapy for Stage II Chemotherapy. J Clin Oncol. 2004, Aug 2015. 22 (16): 3408-3419.
• Andre T, Boni G, Mounedji-Boudiaf L. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. N Engl J Med 2004; 350: 2343-2351.
• Twelves CJ. Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial: overview of efficacy, safety, and cost-effectiveness. Clin Colorectal Cancer 2006 Nov; 6(4): 278-287.
• Mayer R, Cutsem EV, Falcone A, et al. Randomized trial of TAS-102 for Refractory Metastatic Colorectal Cancer. N Engl J Med 2015; 372: 1909-1919.
• Cook NR, Lee IM, Zhang SM et al. Alternate-day low-dose aspirin and cancer risk: Long-term observational follow-up of a randomized trial. Ann Intern Med. 2013 Jul 16; 159(2): 77-85.
• National Cancer Institute Cancer Trends Progress Report: colorectal cancer. https://progressreport.cancer.gov/detection/colorectal_cancer. Accessed April 29, 2017.