Colon Cancer Is the Third

Colon Cancer is the third most common cancer in men and women in the United States (Cappell, 2005). Colon cancer is often curable by surgery if detected early. Systemic and regional chemotherapy are often used in the treatment of patients with metastatic colon cancer. Radiotherapy is used in cases of rectal cancer to reduce the risk of local recurrence. Long-term survival is related to the stage of disease. Efforts are underway to develop better screening strategies and novel therapies to improve patient survival rates and to minimize toxicity.

Pathophysiology The majority of colon cancers are adenocarcinomas (Buda & Pignatelli, 2004). Chromosome arm 18q deletions are a later event associated with cancer development. These deletions typically involve the targets DPC4 and DCC. Chromosome arm 17p losses and tumor suppressor p53 mutations are common events in late-stage colon cancer. Bcl2 overexpression leading to inhibition of cell death signaling has been observed as a relatively early event in colon cancer development.

Another predisposing condition is hereditary nonpolyposis colon cancer, which is a condition in which individuals inherit a mutation in one of several genes involved in DNA mismatch repair, including MSH2, MLH1, and PMS2 (Guimbaud & Selves, 2003). Colon Cancer Risk Factors Several risk factors have been associated with colon cancer. Colonic polyps, which occur with increasing age, represent a risk for colon cancer development (Kronborg, 2004). Increasing age and a lower intake of folate have been associated with mutations of the Ki-ras oncogene, which are found commonly in colon cancer.

Fat content of the diet has been associated with increased risk of colon cancer. Weak evidence suggests that soy food or isoflavones in the diet protect a person from colon cancer. Exercise is believed to reduce the risk of colon cancer. Women who are postmenopausal and who have never used hormone replacement therapy have a higher risk of colon, but not rectal, cancer than do women who are premenopausal and of the same age, sociocultural class, and dietary habits.

No association exists between frequency of bowel movement or laxative use and risk of colon cancer. Colon Cancer Classifications Colon cancer may be classified by severity using the Dukes classification (Rougier, Clavero-Fabri, & Mitry, 1999), which is described below.

Dukes stage a: Carcinoma in situ limited to mucosa or submucosa Dukes stage B: Cancer that extends into the muscularis, into or through the serosa Dukes stage C: Cancer that extends to regional lymph nodes Dukes stage D: Modified classification; cancer that has metastasized to distant sites The overall 5-year survival rate from colon cancer is ~60%. The 5-year survival rate is different for each stage. The staging classification for colon cancer can predict prognosis well. For Dukes stage a tumors involving only the mucosa, the 5-year survival rate exceeds 90%.

However, for metastatic colon cancer, the 5-year survival rate is ~5%. For Dukes stage B. colon cancers, the 5-year survival rate is ~70%. Once the tumor has spread to the lymph nodes, i.e., Dukes stage C, the 5-year survival rate usually ~60% (Rougier et al., 1999). Medical Care An important advance has recently been made regarding the first-line standard therapy of metastatic colon cancer. Both a European trial and a U.S.

trial found that the rate of response to the combination of 5-fluorouracil (5-FU), leucovorin, and irinotecan (CPT11) was higher than that to 5-FU/leucovorin or CPT11 alone {Andre, 2004 #43}. In addition, the higher response rate translated to a greater median survival duration (about 14 mo) with the combination regimen. Standard therapy for metastatic colon cancer is CPT11 plus 5-FU/leucovorin, also known as the Saltz regimen. Diarrhea is the most commonly encountered adverse effect with this regimen. Other adverse effects include mucositis, neutropenia, hair loss, and skin hypersensitivity reactions.

The combination of 5-FU/leucovorin/CPT11 has the potential for severe toxicity, mainly diarrhea leading to dehydration and vascular collapse, in some patients. Standard therapy starts with an approximately 25% decrease in doses of CPT11 and 5-FU and escalate to full doses only if the initial cycle of treatment is well tolerated. Intrahepatic chemotherapy for colon cancer with liver metastasis is intraarterial floxuridine (FUDR).

Following resection of the primary colon cancer and lymph nodes, 2 options for chemotherapy exist: systemic chemotherapy with a standard regimen such as 5-FU/leucovorin/CPT11 or intrahepatic (intraarterial) chemotherapy with FUDR. The second option is worth considering for patients with large or multiple liver lesions because this route results in delivery of a higher dose of chemotherapy to the liver metastases.

The underlying principle is that liver metastases derive their blood supply primarily through the hepatic arterial circulation, whereas normal liver derives most of its blood supply through the portal vein. The major adverse effect of intraarterial FUDR is sclerosing cholangitis, which may be quite severe and may necessitate discontinuation of therapy. Studies have demonstrated a survival advantage for patients with Dukes stage C. colon cancer who receive adjuvant chemotherapy.

The 5-FU-based therapy has been administered in the past according to several schedules, including continuous infusion daily for 5 days every 4 weeks (Mayo Clinic regimen) and weekly for 6 weeks with 2 weeks off (Roswell Park regimen). In terms of patient survival, no study has demonstrated the superiority of daily therapy for 5 days every 4 weeks over weekly therapy for 6 weeks or any other schedule.

Thus, the regimens that can be administered on an outpatient basis (weekly for 6 wk with 2 wk off or daily for 5 days every 4 wk) are the most popular and are widely considered to be essentially equivalent. The classic surgical procedure for colon cancer is anterior resection that involves a "no touch" isolation technique. The abdomen is explored to determine whether the tumor is resectable, and resection is performed segmentally with end-to-end anastomosis. Total colonic resection is performed for patients with familial polyposis and multiple colonic polyps.

Although sulindac appears to influence the morphological appearance of polyps in patients with familial adenomatous polyposis, inducing apparent regression at a dose of 200 mg, it does not influence the progression of polyps toward a malignant pattern. The technology exists to use laparoscopic techniques to achieve colon resection. A recent study reported favorable results with 5 years of follow-up. Sphincter replacement by electrically stimulated skeletal muscle neosphincter and artificial anal sphincter provide a continence option for patients with end-stage fecal incontinence and those requiring abdominoperineal resection.

Partial hepatectomy for colon cancer metastases limited to the liver is a therapeutic option for a subset of patients with recurrent colon cancer that appears to be confined to the liver. Some studies have reported an increased median.