National Cancer Institute


Expert-reviewed information summary about the treatment of colon cancer.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of colon cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Colon Cancer Treatment

General Information About Colon Cancer

Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. Surgery is the primary form of treatment and results in cure in approximately 50% of the patients. Recurrence following surgery is a major problem and is often the ultimate cause of death.

Incidence and Mortality

Estimated new cases and deaths from colon cancer in the United States in 2017:

  • New cases: 95,520 (colon cancer only).
  • Deaths: 50,260 (colon and rectal cancers combined).

Gastrointestinal stromal tumors can occur in the colon. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.)

Anatomy

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, colon, small intestine, rectum, and anus.Anatomy of the lower gastrointestinal system.

Risk Factors

Increasing age is the most important risk factor for most cancers. Other risk factors for colorectal cancer include the following:

  • Family history of colorectal cancer in a first-degree relative.
  • Personal history of colorectal adenomas, colorectal cancer, or ovarian cancer.
  • Hereditary conditions, including familial adenomatous polyposis (FAP) and Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]).
  • Personal history of long-standing chronic ulcerative colitis or Crohn colitis.
  • Excessive alcohol use.
  • Cigarette smoking.
  • Race/ethnicity: African American.
  • Obesity.

Screening

Because of the frequency of the disease, ability to identify high-risk groups, slow growth of primary lesions, better survival of patients with early-stage lesions, and relative simplicity and accuracy of screening tests, screening for colon cancer should be a part of routine care for all adults aged 50 years and older, especially for those with first-degree relatives with colorectal cancer. (Refer to the PDQ summary on Colorectal Cancer Screening for more information.)

Prognostic Factors

The prognosis of patients with colon cancer is clearly related to the following:

  • The degree of penetration of the tumor through the bowel wall.
  • The presence or absence of nodal involvement.
  • The presence or absence of distant metastases.

These three characteristics form the basis for all staging systems developed for this disease.

Other prognostic factors include the following:

  • Bowel obstruction and bowel perforation are indicators of poor prognosis.
  • Elevated pretreatment serum levels of carcinoembryonic antigen (CEA) have a negative prognostic significance.

Many other prognostic markers have been evaluated retrospectively for patients with colon cancer, though most, including allelic loss of chromosome 18q or thymidylate synthase expression, have not been prospectively validated. Microsatellite instability, also associated with HNPCC, has been associated with improved survival independent of tumor stage in a population-based series of 607 patients younger than 50 years with colorectal cancer. Patients with HNPCC reportedly have better prognoses in stage-stratified survival analysis than patients with sporadic colorectal cancer, but the retrospective nature of the studies and possibility of selection factors make this observation difficult to interpret.

Treatment decisions depend on factors such as physician and patient preferences and the stage of the disease, rather than the age of the patient.

Racial differences in overall survival (OS) after adjuvant therapy have been observed, without differences in disease-free survival, suggesting that comorbid conditions play a role in survival outcome in different patient populations.

Follow-up and Survivorship

Limited data and no level 1 evidence are available to guide patients and physicians about surveillance and management of patients after surgical resection and adjuvant therapy. The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend specific surveillance and follow-up strategies.

Following treatment of colon cancer, periodic evaluations may lead to the earlier identification and management of recurrent disease. The impact of such monitoring on overall mortality of patients with recurrent colon cancer, however, is limited by the relatively small proportion of patients in whom localized, potentially curable metastases are found. To date, no large-scale randomized trials have documented an OS benefit for standard, postoperative monitoring program.

CEA is a serum glycoprotein frequently used in the management of patients with colon cancer. A review of the use of this tumor marker suggests the following:

  • A CEA level is not a valuable screening test for colorectal cancer because of the large numbers of false-positive and false-negative reports.
  • Postoperative CEA testing should be restricted to patients who would be candidates for resection of liver or lung metastases.
  • Routine use of CEA levels alone for monitoring response to treatment should not be recommended.

The optimal regimen and frequency of follow-up examinations are not well defined because the impact on patient survival is not clear and the quality of data is poor.

Factors Associated with Recurrence

Diet and exercise

No prospective randomized trials have demonstrated an improvement in outcome with a specific diet or exercise regimen; however, cohort studies suggest that diet or exercise regimen may improve outcome. The cohort studies contain multiple opportunities for unintended bias, and caution is needed when using the data from them.

Two prospective observational studies were performed with patients enrolled on the Cancer and Leukemia Group B ( [NCT00003835] trial), which was an adjuvant chemotherapy trial for patients with stage III colon cancer. In this trial, patients in the lowest quintile of the Western dietary pattern compared with those patients in the highest quintile experienced an adjusted hazard ratio (HR) for disease-free survival of 3.25 (95% confidence interval [CI], 2.04–5.19; < .001) and an OS of 2.32 (95% CI, 1.36–3.96; < .001). Additionally, findings included that stage III colon cancer patients in the highest quintile of dietary glycemic load experienced an adjusted HR for OS of 1.76 (95% CI, 1.22–2.54; < .001) compared with those in the lowest quintile. Subsequently, in the Cancer Prevention Study II Nutrition Cohort, among 2,315 participants diagnosed with colorectal cancer, the degree of red and processed meat intake before diagnosis was associated with a higher risk of death (relative risk [RR], 1.29; 95% CI, 1.05–1.59; = .03), but red meat consumption after diagnosis was not associated with overall mortality.[]

A meta-analysis of seven prospective cohort studies evaluating physical activity before and after a diagnosis of colorectal cancer demonstrated that patients who participated in any amount of physical activity before diagnosis had a RR of 0.75 (95% CI, 0.65–0.87; < .001) for colorectal cancer-specific mortality compared with patients who did not participate in any physical activity. Patients who participated in a high amount of physical activity (vs. a low amount) before diagnosis had a RR of 0.70 (95% CI, 0.56–0.87; = .002). Patients who participated in any physical activity (compared with no activity) after diagnosis had a RR of 0.74 (95% CI, 0.58–0.95; = .02) for colorectal cancer-specific mortality. Those who participated in a high amount of physical activity (vs. a low amount) after diagnosis had a RR of 0.65 (95% CI, 0.47–0.92; = .01).[]

Aspirin

A prospective cohort study examined the use of aspirin after a colorectal cancer diagnosis. Regular users of aspirin after a diagnosis of colorectal cancer experienced an HR of colon cancer-specific survival of 0.71 (95% CI, 0.65–0.97) and an OS of 0.79 (95% CI, 0.65–0.97).[] One study evaluated 964 patients with rectal or colon cancer from the Nurse’s Health Study and the Health Professional Follow-up Study. Among patients with -mutant colorectal cancer, regular use of aspirin was associated with an HR for OS of 0.54 (95% CI, 0.31–0.94; = .01)[]

Related Summaries

Other PDQ summaries containing information related to colon cancer include the following:

  • Colorectal Cancer Prevention
  • Colorectal Cancer Screening
  • Genetics of Colorectal Cancer
  • Unusual Cancers of Childhood Treatment (childhood cancer of the colon)

Cellular Classification of Colon Cancer

Histologic types of colon cancer include the following:

  • Adenocarcinoma (most colon cancers).
    • Mucinous (colloid) adenocarcinoma.
    • Signet ring adenocarcinoma.
  • Scirrhous tumors.
  • Neuroendocrine. Tumors with neuroendocrine differentiation typically have a poorer prognosis than pure adenocarcinoma variants.

Stage Information for Colon Cancer

Treatment decisions should be made with reference to the TNM classification rather than to the older Dukes or the Modified Astler-Coller classification schema.

The American Joint Committee on Cancer (AJCC) and a National Cancer Institute–sponsored panel recommended that at least 12 lymph nodes be examined in patients with colon and rectal cancer to confirm the absence of nodal involvement by tumor. This recommendation takes into consideration that the number of lymph nodes examined is a reflection of the aggressiveness of lymphovascular mesenteric dissection at the time of surgical resection and the pathologic identification of nodes in the specimen. Retrospective studies demonstrated that the number of lymph nodes examined in colon and rectal surgery may be associated with patient outcome.

AJCC Stage Groupings and TNM Definitions

The AJCC has designated staging by TNM classification to define colon cancer. The same classification is used for both clinical and pathologic staging.

Treatment Option Overview for Colon Cancer

Primary Surgical Therapy

Standard treatment for patients with colon cancer has been open surgical resection of the primary and regional lymph nodes for localized disease.

The role of laparoscopic techniques in the treatment of colon cancer has been examined in two studies.

Evidence (laparoscopic techniques):

Surgery is curative in 25% to 40% of highly selected patients who develop resectable metastases in the liver and lung. Improved surgical techniques and advances in preoperative imaging have allowed for better patient selection for resection.

Adjuvant Chemotherapy

The potential value of adjuvant chemotherapy for patients with stage II colon cancer is controversial. Pooled analyses and meta-analyses have suggested a 2% to 4% improvement in OS for patients treated with adjuvant fluorouracil (5-FU)–based therapy compared with observation. (Refer to the Stage II Colon Cancer Treatment section of this summary for more information.)

Prior to 2000, 5-FU was the only useful cytotoxic chemotherapy in the adjuvant setting for patients with stage III colon cancer. Since 2000, capecitabine has been established as an equivalent alternative to 5-FU and leucovorin (5-FU/LV). The addition of oxaliplatin to 5-FU/LV has been shown to improve OS compared with 5-FU/LV alone. (Refer to the Stage III Colon Cancer Treatment section of this summary for more information.)

Chemotherapy regimens

Table 8 describes the chemotherapy regimens used to treat colon cancer.

Adjuvant Radiation Therapy

While combined modality therapy with chemotherapy and radiation therapy has a significant role in the management of patients with rectal cancer (below the peritoneal reflection), the role of adjuvant radiation therapy for patients with colon cancer (above the peritoneal reflection) is not well defined. Patterns-of-care analyses and single-institution retrospective reviews suggest a role for radiation therapy in certain high-risk subsets of colon cancer patients (e.g., T4, tumor location in immobile sites, local perforation, obstruction, and residual disease postresection).

Evidence (adjuvant radiation therapy):

Adjuvant radiation therapy has no current standard role in the management of patients with colon cancer following curative resection, although it may have a role for patients with residual disease.

Stage 0 Colon Cancer Treatment

Stage 0 colon cancer is the most superficial of all the lesions and is limited to the mucosa without invasion of the lamina propria. Because of its superficial nature, the surgical procedure may be limited.

Standard Treatment Options for Stage 0 Colon Cancer

Surgery

Standard treatment options for stage 0 colon cancer include the following:

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage 0 colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Stage I Colon Cancer Treatment

Because of its localized nature, stage I colon cancer has a high cure rate.

Standard Treatment Options for Stage I Colon Cancer

Surgery

Standard treatment options for stage I colon cancer include the following:

Evidence (laparoscopic techniques):

The role of laparoscopic techniques in the treatment of colon cancer was examined in a multicenter, prospective, randomized trial ( [NCT00002575]) comparing laparoscopic-assisted colectomy (LAC) with open colectomy.

  • Three-year recurrence rates and 3-year overall survival rates were similar in the two groups. (Refer to the Primary Surgical Therapy section in the Treatment Option Overview section of this summary for more information.)
  • The quality-of-life component of this trial has been published and minimal short-term quality-of-life benefits with LAC were reported.[]

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Stage II Colon Cancer Treatment

Standard Treatment Options for Stage II Colon Cancer

Surgery

Standard treatment options for stage II colon cancer include the following:

Evidence (laparoscopic techniques):

The role of laparoscopic techniques in the treatment of colon cancer was examined in a multicenter, prospective, randomized trial ( [NCT00002575]) comparing laparoscopic-assisted colectomy (LAC) to open colectomy.

  • Three-year recurrence rates and 3-year overall survival (OS) rates were similar in the two groups. (Refer to the Primary Surgical Therapy section in the Treatment Option Overview section of this summary for more information.)
  • The quality-of-life component of this trial has been published and minimal short-term quality-of-life benefits with LAC were reported.[]

Treatment Options Under Clinical Evaluation

Adjuvant chemotherapy

The potential value of adjuvant chemotherapy for patients with stage II colon cancer remains controversial. Although subgroups of patients with stage II colon cancer may be at higher-than-average risk for recurrence (including those with anatomic features such as tumor adherence to adjacent structures, perforation, complete obstruction), evidence is inconsistent that adjuvant 5-fluorouracil (5-FU)–based chemotherapy is associated with an improved OS compared with surgery alone.

Features in patients with stage II colon cancer that are associated with an increased risk of recurrence include the following:

  • Inadequate lymph node sampling.
  • T4 disease.
  • Involvement of the visceral peritoneum.
  • A poorly differentiated histology.

The decision to use adjuvant chemotherapy for patients with stage II colon cancer is complicated and requires thoughtful consideration by both patients and their physicians. Adjuvant therapy is not indicated for most patients unless they are entered into a clinical trial.

Evidence (adjuvant chemotherapy):

Based on these data, the American Society of Clinical Oncology issued a guideline stating “direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer.”

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage II colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Stage III Colon Cancer Treatment

Stage III colon cancer denotes lymph node involvement. Studies have indicated that the number of lymph nodes involved affects prognosis; patients with one to three involved nodes have a significantly better survival than those with four or more involved nodes.

Standard Treatment Options for Stage III Colon Cancer

Standard treatment options for stage III colon cancer include the following:

Surgery

Surgery for stage III colon cancer is wide surgical resection and anastomosis.

Evidence (laparoscopic techniques):

The role of laparoscopic techniques in the treatment of colon cancer was examined in a multicenter, prospective, randomized trial ( [NCT00002575]) comparing laparoscopic-assisted colectomy (LAC) with open colectomy.

  • Three-year recurrence rates and 3-year overall survival (OS) rates were similar in the two groups. (Refer to the Primary Surgical Therapy section in the Treatment Option Overview section of this summary for more information.)
  • The quality-of-life component of this trial has been published and minimal short-term quality-of-life benefits with LAC were reported.[]

Adjuvant chemotherapy

Chemotherapy regimens prior to 2000

Prior to 2000, 5 fluorouracil (5-FU) was the only useful cytotoxic chemotherapy in the adjuvant setting for patients with stage III colon cancer. Many of the early randomized studies of 5-FU in the adjuvant setting failed to show a significant improvement in survival for patients. These trials employed 5-FU alone or 5-FU-semustine.

Evidence (5-FU alone and 5-FU-semustine):

Chemotherapy regimens after 2000

Capecitabine

Capecitabine is an oral fluoropyrimidine that undergoes a three-step enzymatic conversion to 5-FU with the last step occurring in the tumor cell. For patients with metastatic colon cancer, two studies have demonstrated the equivalence of capecitabine to 5-FU/LV.

For patients with stage III colon cancer, capecitabine provides equivalent outcome to intravenous 5-FU/LV.

Evidence (capecitabine):

Oxaliplatin

Oxaliplatin has significant activity when combined with 5-FU/LV in patients with metastatic colorectal cancer.

Evidence (oxaliplatin):

FOLFOX has become the reference standard for the next generation of clinical trials for patients with stage III colon cancer.

Treatment Options Under Clinical Evaluation

Eligible patients should be considered for entry into carefully controlled clinical trials comparing various postoperative chemotherapy regimens.

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Stage IV and Recurrent Colon Cancer Treatment

Stage IV colon cancer denotes distant metastatic disease. Treatment of recurrent colon cancer depends on the sites of recurrent disease demonstrable by physical examination and/or radiographic studies. In addition to standard radiographic procedures, radioimmunoscintography may add clinical information that may affect management. Such approaches have not led to improvements in long-term outcome measures such as survival.

Treatment Options for Stage IV and Recurrent Colon Cancer

Treatment options for stage IV and recurrent colon cancer include the following:

Treatment of Liver Metastasis

Approximately 50% of colon cancer patients will be diagnosed with hepatic metastases, either at the time of initial presentation or as a result of disease recurrence. Although only a small proportion of patients with hepatic metastases are candidates for surgical resection, advances in tumor ablation techniques and in both regional and systemic chemotherapy administration provide for a number of treatment options. These include the following:

  • Surgery.
  • Neoadjuvant chemotherapy.
  • Local ablation.
  • Adjuvant chemotherapy.
  • Intra-arterial chemotherapy.

Surgery

Hepatic metastasis may be considered to be resectable based on the following:

  • Limited number of lesions.
  • Intrahepatic locations of lesions.
  • Lack of major vascular involvement.
  • Absent or limited extrahepatic disease.
  • Sufficient functional hepatic reserve.

For patients with hepatic metastasis that is considered to be resectable, a negative margin resection resulted in 5-year survival rates of 25% to 40% in mostly nonrandomized studies. Improved surgical techniques and advances in preoperative imaging have allowed for better patient selection for resection. In addition, multiple studies with multiagent chemotherapy have demonstrated that patients with metastatic disease isolated to the liver, which historically would be considered unresectable, can occasionally be made resectable after the administration of chemotherapy.

Neoadjuvant chemotherapy for unresectable liver metastases

Patients with hepatic metastases that are deemed unresectable will occasionally become candidates for resection if they have a good response to chemotherapy. These patients have 5-year survival rates similar to patients who initially had resectable disease. There is no consensus on the best regimen to use to convert unresectable isolated liver metastases to resectable liver metastases.

Local ablation

Radiofrequency ablation has emerged as a safe technique (2% major morbidity and <1% mortality rate) that may provide for long-term tumor control. Radiofrequency ablation and cryosurgical ablation remain options for patients with tumors that cannot be resected and for patients who are not candidates for liver resection.

Other local ablative techniques that have been used to manage liver metastases include embolization and interstitial radiation therapy. Patients with limited pulmonary metastases, and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly-selected patients.

Adjuvant or neoadjuvant chemotherapy for resectable liver metastases

The role of adjuvant chemotherapy after potentially curative resection of liver metastases is uncertain.

Evidence (adjuvant or neoadjuvant chemotherapy for resectable liver metastases):

In the era before the use of FOLFOX (folinic acid [LV], 5-fluorouracil [5-FU], and oxaliplatin) and FOLFIRI (5-FU/leucovorin [LV]/irinotecan), two trials attempted to randomly assign patients after resection of liver metastases to 5-FU/ or observation, but both studies were closed early because of poor accrual.

In the era of multiagent chemotherapy, two subsequent studies evaluated its role in the adjuvant setting following resection of liver metastases from colorectal cancer.

There is no level 1 evidence demonstrating that perioperative or postoperative chemotherapy improves OS for patients undergoing resection of liver metastases. Nevertheless, on the basis of post hoc subset analyses of the EORTC study, some physicians feel perioperative or postoperative therapy is reasonable in this setting.

Intra-arterial chemotherapy after liver resection

Hepatic intra-arterial chemotherapy with floxuridine for liver metastases has produced higher overall response rates but no consistent improvement in survival when compared with systemic chemotherapy. A meta-analysis of the randomized studies, which were all done in the era when only fluoropyrimidines were available for systemic therapy, did not demonstrate a survival advantage.

Evidence (intra-arterial chemotherapy after liver resection):

Two trials evaluated hepatic arterial floxuridine in the adjuvant setting after liver resection.

Further studies are required to evaluate this treatment approach and to determine whether more effective systemic combination chemotherapy alone may provide similar results compared with hepatic intra-arterial therapy plus systemic treatment.

Several studies show increased local toxic effects with hepatic infusional therapy, including liver function abnormalities and fatal biliary sclerosis.

Treatment of Stage IV and Recurrent Colon Cancer

  • Surgery.
  • Chemotherapy and targeted therapy.

Surgery

Treatment of patients with recurrent or advanced colon cancer depends on the location of the disease. For patients with locally recurrent and/or liver-only and/or lung-only metastatic disease, surgical resection, if feasible, is the only potentially curative treatment.

Chemotherapy and targeted therapy

Currently, there are thirteen active U.S. Food and Drug Administration (FDA)-approved drugs for patients with metastatic colorectal cancer that are used alone and in combination with other drugs:

  • 5-FU.
  • Capecitabine.
  • Irinotecan.
  • Oxaliplatin.
  • Bevacizumab.
  • FOLFOXIRI (irinotecan, oxaliplatin, LV, and 5-FU).
  • Cetuximab.
  • Aflibercept.
  • Ramucirumab.
  • Panitumumab.
  • Anti-epidermal growth factor receptor (EGFR) antibody versus anti-vascular endothelial growth factor (VEGF) antibody with first-line chemotherapy.
  • Regorafenib.
  • TAS-102.

5-FU

When 5-FU was the only active chemotherapy drug, trials in patients with locally advanced, unresectable, or metastatic disease demonstrated partial responses and prolongation of the time-to-progression (TTP) of disease, and improved survival and quality of life for patients who received chemotherapy versus best supportive care. Several trials have analyzed the activity and toxic effects of various 5-FU/LV regimens using different doses and administration schedules and showed essentially equivalent results with a median survival time in the 12-month range.

Capecitabine

Before the advent of multiagent chemotherapy, two randomized studies demonstrated that capecitabine was associated with equivalent efficacy when compared with the Mayo Clinic regimen of 5-FU/LV.[]

Irinotecan

Three randomized studies demonstrated improved response rates, PFS, and OS when irinotecan or oxaliplatin was combined with 5-FU-leucovorin.

Evidence (irinotecan):

Since the publication of these studies, the use of either FOLFOX or FOLFIRI is considered acceptable for first-line treatment of patients with metastatic colorectal cancer.

When using an irinotecan-based regimen as first-line treatment of metastatic colorectal cancer, FOLFIRI is preferred.[]

Oxaliplatin

Randomized phase III trials have addressed the equivalence of substituting capecitabine for infusional 5-FU. Two phase III studies have evaluated FUOX versus CAPOX.

Evidence (oxaliplatin):

When using an oxaliplatin-based regimen as first-line treatment of metastatic colorectal cancer, a CAPOX regimen is not inferior to a FUOX regimen.

Before the availability of cetuximab, panitumumab, bevacizumab, and aflibercept as second-line therapy, second-line chemotherapy with irinotecan in patients treated with 5-FU/LV as first-line therapy demonstrated improved OS when compared with either infusional 5-FU or supportive care.

Similarly, a phase III trial randomly assigned patients who progressed on irinotecan and 5-FU/LV to bolus and infusional 5-FU/LV (LV5FU2), single-agent oxaliplatin, or FOLFOX-4. The median TTP for FOLFOX-4 versus LV5FU2 was 4.6 months versus 2.7 months (stratified log-rank test, 2-sided < .001).[]

Bevacizumab

Bevacizumab is a partially humanized monoclonal antibody that binds to vascular endothelial growth factor. Bevacizumab can reasonably be added to either FOLFIRI or FOLFOX for patients undergoing first-line treatment of metastatic colorectal cancer.

Evidence (bevacizumab):

Based on these studies, bevacizumab can reasonably be added to either FOLFIRI or FOLFOX for patients undergoing first-line treatment of metastatic colorectal cancer. A major question was whether the use of bevacizumab after first-line therapy was warranted when bevacizumab was used as a component of first-line therapy. At the 2012 American Society of Clinical Oncology Annual Meeting, data were presented from a randomized, controlled trial. In the trial, 820 patients with metastatic colorectal cancer, after progressing on first-line chemotherapy that included bevacizumab, were randomly assigned to chemotherapy without bevacizumab or chemotherapy with bevacizumab. Patients who received bevacizumab experienced an improved OS compared with the patients who did not receive bevacizumab. Median OS was 11.2 months for patients who received bevacizumab plus chemotherapy and 9.8 months for patients who received chemotherapy without bevacizumab (HR, 0.81; 95% CI, 0.69–0.94; unstratified log-rank test, = .0062). Median PFS was 5.7 months for patients who received bevacizumab plus chemotherapy and 4.1 months for those who received chemotherapy without bevacizumab (HR, 0.68; 95% CI, 0.59–0.78; unstratified log-rank test, < .0001). []

FOLFOXIRI

Evidence (FOLFOXIRI):

Cetuximab

Cetuximab is a partially humanized monoclonal antibody against the EGFR. Because cetuximab affects tyrosine kinase signaling at the surface of the cell membrane, tumors with mutations causing activation of the pathway downstream of the EGFR, such as mutations, are not sensitive to its effects. The addition of cetuximab to multiagent chemotherapy improves survival in patients with colon cancers that lack a mutation (i.e., wild type). Importantly, patients with mutant tumors may experience worse outcome when cetuximab is added to multiagent chemotherapy regimens containing bevacizumab.

Evidence (cetuximab):

Aflibercept

Aflibercept is a novel anti-VEGF molecule and has been evaluated as a component of second-line therapy in patients with metastatic colorectal cancer.

Evidence (afilbercept):

Ramucirumab

Ramucirumab is a fully humanized monoclonal antibody that binds to vascular endothelial growth factor receptor-2 (VEGFR-2).

Evidence (ramucirumab):

Panitumumab

Panitumumab is a fully humanized antibody against the EGFR. The FDA approved panitumumab for use in patients with metastatic colorectal cancer refractory to chemotherapy. In clinical trials, panitumumab demonstrated efficacy as a single agent or in combination therapy, which was consistent with the effects on PFS and OS with cetuximab. There appears to be a consistent class effect.

Evidence (panitumumab):

Anti-EGFR antibody versus anti-VEGF antibody with first-line chemotherapy

In the management of patients with stage IV colorectal cancer, it is unknown whether patients with wild-type cancer should receive an anti-EGFR antibody with chemotherapy or an anti-VEGF antibody with chemotherapy. Two studies attempted to answer this question.

Evidence (anti-EGFR antibody vs. anti-VEGF antibody with first-line chemotherapy)

On the basis of these two studies, no apparent significant difference is evident about starting treatment with chemotherapy/bevacizumab or chemotherapy/cetuximab in patients with wild-type metastatic colorectal cancer. However, in patients with wild-type cancer, administration of an anti-EGFR antibody at some point in the course of management improves OS.

Regorafenib

Regorafenib is an inhibitor of multiple tyrosine kinase pathways including VEGF. In September 2012, the FDA granted approval for the use of regorafenib in patients who had progressed on previous therapy.

Evidence (regorafenib):

TAS-102

TAS-102 (Lonsurf) is an orally administered combination of a thymidine-based nucleic acid analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride. Trifluridine, in its triphosphate form, inhibits thymidylate synthase; therefore, trifluridine, in this form, has an anti-tumor effect. Tipiracil hydrochloride is a potent inhibitor of thymidine phosphorylase, which actively degrades trifluridine. The combination of trifluridine and tipiracil allows for adequate plasma levels of trifluridine.

Evidence (TAS-102):

TAS-102 was approved by the FDA for the treatment of metastatic colorectal cancer patients, based on the results of the RECOURSE trial.

Treatment Options Under Clinical Evaluation

Treatment options under clinical evaluation for stage IV and recurrent colon cancer include the following:

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage IV colon cancer and recurrent colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Changes to This Summary (08/18/2017)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Stage IV and Recurrent Colon Cancer Treatment

An editorial change was made to this section.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of colon cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Colon Cancer Treatment are:

  • Russell S. Berman, MD (New York University School of Medicine)
  • David P. Ryan, MD (Massachusetts General Hospital)
  • Jennifer Wo, MD (Massachusetts General Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Colon Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated . Available at: https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq. Accessed . [PMID: 26389297]

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Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.

Blogs

Webucation: Colon Cancer Screening
by OncoLink Team
February 9, 2015

Your Friend the Colonoscopy
by Rodney Warner, JD
March 25, 2016

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