COLON CANCERPractice EssentialsColon cancer is the most common type of gastrointestinal cancer. It is a multifactorial disease process, with etiology encompassing genetic factors, environmental exposures (including diet), and inflammatory conditions of the digestive tract. Essential update: Study suggests long-term colorectal cancer mortality reduced following adenoma removalUsing data from Norways national cancer and cause-of-death registries, Lberg et al found that, compared with the general Norwegian population, the mortality rate from colorectal cancer was lower in patients who had undergone removal of low-risk colorectal adenomas and moderately higher in patients in whom high-risk adenomas had been removed. The study involved 40,826 patients who had undergone adenoma removal. During follow-up (median period, 7.7 years), 141 patients who had had low-risk adenomas and 242 patients who had had high-risk adenomas died of colorectal cancer. Compared with expected colorectal cancer deaths in the general population, this gave the low-risk and high-risk adenoma patients standardized incidence-based mortality ratios of 0.75 and 1.16, respectively.[1] Signs and symptomsColon cancer is now often detected during screening procedures. Other common clinical presentations include the following: Iron-deficiency anemia Rectal bleeding Abdominal pain Change in bowel habits Intestinal obstruction or perforationPhysical findings may include the following: Early disease: Nonspecific findings (fatigue, weight loss) or none at all More advanced disease: Abdominal tenderness, macroscopic rectal bleeding, palpable abdominal mass, hepatomegaly, ascitesSee Clinical Presentation for more detail.DiagnosisLaboratory studies that may be helpful include the following: Complete blood count Chemistries and liver function tests Serum carcinoembryonic antigenImaging studies that may facilitate staging include the following: Chest radiography Chest computed tomography Abdominal barium study Abdominal/pelvic CT Contrast ultrasonography of the abdomen and liver Abdominal/pelvic MRI Positron emission tomography, including fusion PET-CT scanOther procedures that may be warranted include the following: Colonoscopy Sigmoidoscopy Biopsy of suspicious lesions Double-contrast barium enemaCurrent TNM classification is as follows: Tx No description of tumor extent possible, because of incomplete information Tis In situ carcinoma; tumor involves only muscularis mucosa T1 Cancer has grown through muscularis mucosa and extends into submucosa T2 Cancer has grown through submucosa and extends into muscularis propria T3 Cancer has grown through muscularis propria and into outermost layers of colon but not through them; it has not reached any nearby organs or tissues T4a Cancer has grown through serosa (visceral peritoneum) T4b Cancer has grown through wall of colon and is attached to or invades nearby tissues or organs Nx No description of lymph node involvement possible, because of incomplete information N0 No cancer in nearby lymph nodes N1a Cancer cells found in 1 nearby lymph node N1b Cancer cells found in 2-3 nearby lymph nodes N1c Small deposits of cancer cells found in areas of fat near lymph nodes, but not in lymph nodes themselves N2a Cancer cells found in 4-6 nearby lymph nodes N2b Cancer cells found in 7 or more nearby lymph nodes M0 No distant spread seen M1a Cancer has spread to 1 distant organ or set of distant lymph nodes M1b Cancer has spread to more than 1 distant organ or set of distant lymph nodes, or has spread to distant parts of the peritoneum Staging is as follows:

ManagementSurgery is the only curative modality for localized colon cancer (stage I-III). Surgical resection potentially provides the only curative option for patients with limited metastatic disease in liver and/or lung (stage IV disease). Surgical options include the following: Right hemicolectomy: For lesions in the cecum and right colon Extended right hemicolectomy: For lesions in the proximal or middle transverse colon Left hemicolectomy: For lesions in the splenic flexure and left colon Sigmoid colectomy: For sigmoid colon lesions Total abdominal colectomy with ileorectal anastomosis: For selected patients with hereditary nonpolyposis colon cancer, attenuated familial adenomatous polyposis, metachronous cancers in separate colon segments, or acute malignant colon obstructions with unknown status of the proximal bowel Other therapeutic options for patients who are not surgical candidates include the following: Cryotherapy Radiofrequency ablation Hepatic arterial infusion of chemotherapeutic agentsRegimens used for systemic chemotherapy may include the following: 5-Fluorouracil (5-FU) Capecitabine Tegafur Oxaliplatin Irinotecan Combinations of multiple agents (eg, capecitabine or 5-FU with oxaliplatin, 5-FU with leucovorin and oxaliplatin)Regimens used for adjuvant (postoperative) chemotherapy commonly include 5-FU with leucovorin or capecitabine, either alone or in combination with oxaliplatin.[2, 3, 4] Biologic agents employed to treat colon cancer include the following: Bevacizumab (Avastin) Cetuximab (Erbitux) Panitumumab (Vectibix) Regorafenib (Stivarga) Ziv-aflibercept (Zaltrap)

\Medication Summary5-Fluorouracil remains the backbone of chemotherapy regimens for colon cancer, both in the adjuvant and metastatic setting. In addition to 5-fluorouracil, oral fluoropyrimidines such as capecitabine (Xeloda) and tegafur are increasingly used as monotherapy or in combination with oxaliplatin (Eloxatin) and irinotecan (Camptosar). Some of the standard combination regimens employ prolonged continuous infusion of fluorouracil (FOLFIRI, FOLFOX)[113] or capecitabine (CAPOX, XELOX, XELIRI).[114, 115] Adjuvant therapy regimensCommonly used combination regimens for adjuvant therapy include the following:5-Fluorouracil + leucovorin (weekly schedule, low-dose leucovorin) 5-Fluorouracil: 500 mg/m2 intravenous (IV) weekly for 6 weeks Leucovorin: 20 mg/m2 IV weekly for 6 weeks, administered before 5-fluorouracil Repeat cycle every 8 weeks for a total of 24 weeksLV5FU2 (de Gramont regimen) 5-Fluorouracil: 400 mg/m2 IV bolus, followed by 600 mg/m2 IV continuous infusion for 22 hours on days 1 and 2 Leucovorin: 200 mg/m2 IV on days 1 and 2 as a 2-hour infusion before 5-fluorouracil Repeat cycle every 2 weeks for a total of 12 cyclesOxaliplatin + 5-fluorouracil + leucovorin (FOLFOX4) Oxaliplatin: 85 mg/m2 IV on day 1 5-Fluorouracil: 400 mg/m2 IV bolus, followed by 600 mg/m2 IV continuous infusion for 22 hours on days 1 and 2 Leucovorin: 200 mg/m2 IV on days 1 and 2 as a 2-hour infusion before 5-fluorouracil Repeat cycle every 2 weeks for a total of 12 cyclesOxaliplatin + 5-fluorouracil + leucovorin (FOLFOX6) Oxaliplatin: 85-100 mg/m2 IV on day 1 5-Fluorouracil: 400 mg/m2 IV bolus on day 1, followed by 2400 mg/m2 IV continuous infusion for 46 hours Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, before 5-fluorouracil Repeat cycle every 2 weeksMetastatic disease regimensCommonly used combination regimens for metastatic disease include the following:Irinotecan + 5-fluorouracil + leucovorin (FOLFIRI regimen) Irinotecan: 180 mg/m2 IV on day 1 5-Fluorouracil: 400 mg/m2 IV bolus on day 1, followed by 2400 mg/m2 IV continuous infusion for 46 hours Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, prior to 5-fluorouracil Repeat cycle every 2 weeksOxaliplatin + 5-fluorouracil + leucovorin (FOLFOX6) Oxaliplatin: 85-100 mg/m2 IV on day 1 5-Fluorouracil: 400 mg/m2 IV bolus on day 1, followed by 2400 mg/m2 IV continuous infusion for 46 hours Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, before 5-fluorouracil Repeat cycle every 2 weeksOxaliplatin + 5-fluorouracil + leucovorin (mFOLFOX7) Oxaliplatin: 100 mg/m2 IV on day 1 5-Fluorouracil: 3000 mg/m2 IV continuous infusion on day 1 for 46 hours Leucovorin: 400 mg/m2 IV on day 1 as a 2-hour infusion, before 5-fluorouracil Repeat cycle every 2 weeksCapecitabine + oxaliplatin (XELOX) Capecitabine: 850-1000 mg/m2 PO bid on days 1-14 Oxaliplatin: 100-130 mg/m2 IV on day 1 Repeat cycle every 21 daysFOLFOX4 + bevacizumab Oxaliplatin: 85 mg/m2 IV on day 1 5-Fluorouracil: 400 mg/m2 IV bolus, followed by 600 mg/m2 IV continuous infusion on days 1 and 2 Leucovorin: 200 mg/m2 IV on days 1 and 2 as a 2-hour infusion before 5-fluorouracil Bevacizumab: 10 mg/kg IV every 2 weeks Repeat cycle every 2 weekshttp://emedicine.medscape.com/article/277496-overview

Cancer Prev Res (Phila). 2011 Aug;4(8):1172-80. doi: 10.1158/1940-6207.CAPR-10-0403.C-reactive protein and risk of colorectal adenoma according to celecoxib treatment.Chan AT1, Sima CS, Zauber AG, Ridker PM, Hawk ET, Bertagnolli MM.Author information AbstractInflammation, as measured by the circulating inflammatory marker high-sensitivity C-reactive protein (hsCRP), has been associated with cardiovascular disease. However, data about CRP and risk of colorectal cancer have been conflicting. The Adenoma Prevention with Celecoxib (APC) trial showed that the anti-inflammatory drug celecoxib prevents recurrence of colorectal adenoma but increases risk of cardiovascular events. We examined whether serum hsCRP modified these results. We measured hsCRP from serum specimens provided at study entry by patients enrolled in the APC trial. Patients were stratified according to use of low-dose aspirin, randomized to receive 3 years of treatment with placebo, 200-mg-bid celecoxib, or 400-mg-bid celecoxib, and underwent follow-up colonoscopies at years 1 and 3. Among 1,680 patients, the estimated 3-year cumulative incidence of adenoma was 42% for patients with hsCRP 3 mg/L. The effect of celecoxib on adenoma recurrence did not vary among patients with high (>3 mg/L) compared with low (3 mg/L) hsCRP. However, among patients with high hsCRP, the RR of cardiovascular events compared with placebo was 2.27 (95% CI = 0.72-7.14) for those randomized to celecoxib 200-mg-bid and 3.28 (95% CI = 1.09-9.91) for 400-mg-bid. In contrast, among patients with low hsCRP, the corresponding RRs were 0.99 (95% CI = 0.53-1.83) and 1.11 (95% CI = 0.61-2.02). hsCRP may predict risk of celecoxib-associated cardiovascular toxicity but not adenoma recurrence or celecoxib treatment efficacy. Patients with low hsCRP may be a subgroup with a favorable risk-benefit profile for celecoxib chemoprevention.