Stage IV Colon Cancer

Overview

Colon cancer is classified as Stage IV if the final evaluation following surgical removal of the cancer shows that the cancer has spread to distant locations in the body; this may include the liver, lungs, bones, distant lymph nodes or other sites. While it is commonly thought that patients diagnosed with Stage IV colon cancer have few treatment options, certain patients can still be cured of their cancer, and others can derive significant benefit from additional treatment.

Patients with Stage IV colon cancer can be broadly divided into two groups:

  • Those with widespread, metastatic cancer that cannot be treated with surgery (sometimes called unresectable cancer )
  • Those with cancer that has metastasized to a single site

When the site of metastasis is a single organ (such as the liver), and the cancer is confined to a single defined area within the organ, patients may benefit from local treatment directed at that single metastasis.

The majority of patients diagnosed with Stage IV colon cancer have unresectable or widespread disease. Historically, treatment outcomes for these patients were poor. However, new combinations of chemotherapy drugs and the addition of targeted therapies such as Avastin® (bevacizumab) have improved outcomes.

The following is a general overview of treatment for Stage IV colon cancer. Treatment may consist of surgery, radiation, chemotherapy, targeted therapy, or a combination of these treatment techniques. Multi-modality treatment, which is treatment using two or more techniques, has become an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied.

The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

This section covers the initial, also called first-line, treatment of Stage IV colon cancer. For information about the treatment of cancer that has recurred or progressed after initial treatment, visit Recurrent Colon Cancer.

Chemotherapy for Widespread, Metastatic Colon Cancer

For over 30 years the chemotherapy drug fluorouracil (5-FU) was the standard treatment for metastatic Stage IV colon cancer that had spread to several sites in the body. 5-FU is typically administered with leucovorin, a drug that is similar in structure and function to the essential vitamin folic acid. Leucovorin (LV) enhances the anticancer effects of fluorouracil by helping the chemotherapy drug bind to and stay inside the cell for a greater period of time, producing longer lasting anticancer effects.

More recently, the addition of other drugs to 5-FU/LV has been found to provide additional benefit. Not all patients can tolerate these multi-drug regimens, however, and less intensive regimens are available.

Adding Targeted Therapy to Chemotherapy

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy. Recently approved targeted therapies represent the most novel advance in the treatment of metastatic colorectal cancer in the last few years.

Targeted therapies that have shown a benefit for selected patients with metastatic colorectal cancer include Avastin® (bevacizumab), Erbitux® (cetuximab), and Vectibix® (panitumumab). Avastin blocks a protein (VEGF) that plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Erbitux and Vectibix slow cancer growth by targeting a protein known as EGFR. Cancers with certain gene mutations are unlikely to respond to Erbitux or Vectibix, and tests are available to detect these mutations before treatment decisions are made.

Treatment of Colon Cancer That has Metastasized to a Single Site

Stage IV colon cancer commonly spreads to the liver or the lungs. Some patients who have cancer that has spread to a single area are candidates for surgery to remove the metastases.

Treatment of the liver: When it’s possible to completely surgically remove all liver metastases, surgery is the preferred treatment. Although surgery offers some patients the chance for a cure, a majority of patients with liver metastases are not candidates for surgery because of the size or location of their tumors or their general health. Some of these patients may become candidates for surgery if initial treatment with chemotherapy shrinks the tumors sufficiently. If the tumors continue to be impossible to remove surgically, other liver-directed therapies may be considered. These other therapies include radiofrequency ablation (use of heat to kill cancer cells), cryotherapy (use of cold to kill cancer cells), delivery of chemotherapy directly to the liver, and radiation therapy. Relatively little information is available from clinical trials about the risks and benefits of these other approaches, but they may benefit selected patients.1

Treatment of the Elderly

A large percentage of patients with advanced colorectal cancer are 65 years or older. Because elderly patients commonly have concurrent illnesses or other medical difficulties that are perceived to exacerbate the side effects of chemotherapy, elderly patients are often treated with reduced doses of chemotherapy. Clinical studies have shown, however, that elderly patients get the same benefit from chemotherapy treatment as younger patients.

While a dose reduction or delay may sometimes be necessary, it may also compromise the optimal treatment of some patients. All patients over 65 should be closely monitored for toxic side effects of chemotherapy, especially during their initial chemotherapy administration cycle.

Strategies to Improve Treatment of Stage IV Colon Cancer

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage IV colon cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of Stage IV colon cancer include the following:

New Approaches to Treating Liver Metastases: Researchers continue to explore news ways to treat cancer that has spread to the liver. One approach that is being evaluated is radioembolization This strategy uses radioactive microspheres (small spheres containing radioactive material). The small spheres are injected into vasculature of the liver, where they tend to get lodged in the vasculature responsible for providing blood and nourishment to the cancer cells. While lodged in place, the radioactive substance spontaneously emits radiation to the surrounding cancerous area while minimizing radiation exposure to the healthy portions of the liver.2 Researchers are also exploring alternatives to radiofrequency ablation for the destruction of liver tumors, as well as new approaches to delivering chemotherapy to the liver.

New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research.

New Approaches to Targeted Therapy: Targeted therapies such as Avastin, Erbitux, and Vectibix already play a role in the treatment of selected patients with advanced colorectal cancer, but researchers continue to explore new targeted therapies as well as new ways of using existing drugs. Developing tests to predict which patients are most likely to respond to which drugs is also an important focus of research. Tests to identify certain gene mutations in the cancer are already available, and can help guide the use of Erbitux and Vectibix.

Managing Side Effects: Techniques designed to prevent or control the side effects of cancer and its treatments are called supportive care. Side effects not only cause patients discomfort, but also may prevent the delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that treatment is delivered as planned and that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

Phase I clinical trials: New chemotherapy drugs continue to be developed and evaluated in patients with recurrent cancers in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the best way of administering the drug and whether the drug has any anticancer activity in patients.

References


1 Alsina J, Choti MA. Liver-directed therapies in colorectal cancer. Seminars in Oncology. 2011;38:651-567.

2 Hendlisz A, Van den Eynde M, Peeters M, et al. Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy. Journal of Clinical Oncology. 2010;28:3687-94.

Copyright © 2014 Omni Health Media Colon Cancer Information Center. All Rights Reserved.


< Previous Page


Types Of Cancer
General Cancer Information
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer
Cervical Cancer
Colon Cancer
Esophageal Cancer
Gastric Cancer
Head and Neck Cancer
Hodgkin's Lymphoma
Leukemia
Liver Cancer
Lung Cancer
Melanoma
Mesothelioma
Multiple Myeloma
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Rectal Cancer
Renal Cancer
Sarcoma
Skin Cancer
Testicular Cancer
Thyroid Cancer
Uterine Cancer

Stage III Colon Cancer

Overview

Following surgical removal of colon cancer, the cancer is classified as Stage III if the final pathology report shows that the cancer has penetrated the wall of the colon into the abdominal cavity and invaded any of the local lymph nodes, but cannot be detected in other locations in the body. Stage III adenocarcinoma of the colon is a common and curable cancer. Depending on the features of the cancer, 40-50% of patients are cured without evidence of cancer recurrence following treatment with surgery alone.

Despite undergoing complete surgical removal of the cancer, half of patients with Stage III colon carcinoma experience recurrence of their cancer. This is due to the presence of small amounts of cancer that have spread outside the colon, called micrometastases. It is important to realize that many patients with Stage III disease have micrometastases that are not removed by surgery. These cancer cells cannot be detected with any currently available tests. An effective treatment is needed to eliminate micrometastases and improve the cure rates of Phase III cancer. Efforts are currently underway to find such a therapy.

The following is a general overview of treatment for Stage III colon cancer. Treatment may consist of surgery, chemotherapy, targeted therapy (drugs which act by a different mechanism than chemotherapy to target tumor cells) and/or radiation. Multi-modality treatment, which is treatment using two or more techniques, is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

Adjuvant Chemotherapy Treatment

The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy, and/or targeted therapy. Adjuvant chemotherapy is administered to patients with Stage III colon cancer for the purpose of reducing the risk of cancer recurrence.

Adjuvant treatment with chemotherapy has been shown to reduce the risk of tumor relapse and improve survival among patients with Stage III colon cancer. Since the 1980’s, the mainstay of chemotherapy treatment has been a combination of 5-flourouracil  (5-FU) and leucovorin (LV). More recently, researchers have evaluated the effects of combining 5-FU/LV with other drugs.

Adding Eloxatin® (oxaliplatin) to 5-FU/LV appears to improve outcomes. Eloxatin is a platinum-based chemotherapy drug that was FDA-approved for the adjuvant treatment of Stage III colon cancer in 2004. The combination of Eloxatin with 5-FU/LV may be abbreviated FOLFOX or FLOX, depending on exactly how the drugs are given.

In two large trials, adding Eloxatin increased 3-year disease free survival by 5-7%.  The first trial compared 2,246 patients receiving either FU/LV or FU/LV plus Eloxatin. In patients with Stage III disease, three year disease-free survival was 72% in the FU/LV plus Eloxatin group, compared with 65% in the FU/LV group.1 A more recent trial (NSABP C-07) of 2,492 patients demonstrated 3-year disease free survival rates of 76% in patients receiving FU/LV plus Eloxatin compared with 72% in patients receiving FU/LV.2

Xeloda® (capecitabine) is another treatment that has been FDA-approved for the adjuvant treatment of patients with Stage III colon cancer. Xeloda is a form of the chemotherapy drug 5-FU that is administered orally as a pill, rather than into a vein.

In the treatment of colorectal cancer, Xeloda appears to work as well as 5-FU/LV with fewer side effects.3,4 In addition, oral administration is more convenient since it requires fewer clinic visits—patients receiving Xeloda will make a minimum of eight trips to their clinic, whereas those on 5-FU may make up to 30 trips.5

Treatment of the Elderly

A large percentage of patients with colon cancer are 65 years or older. Sometimes elderly patients and/or their physicians may believe that believe that treatment will be more toxic for elderly patients than it is for their younger counterparts. Due to this perceived intolerability of therapy, elderly patients often do not receive optimal treatment.

To assess the effects of chemotherapy by age, researchers analyzed data from 7 separate clinical trials that were conducted to evaluate adjuvant chemotherapy in patients with Stage II or III colon cancer. Patients were divided into four age groups: 50 years and younger, 51 to 60 years, 61 to 70 years and 70 years and older. In these trials, patients received either surgery alone or surgery followed by adjuvant chemotherapy consisting of either 5-FU plus leucovorin or 5-FU plus levamisole. Five years following treatment, the overall survival rate was 71% for patients treated with adjuvant chemotherapy versus only 64% for those treated with surgery alone. There were no differences in survival rates between the age groups. The incidence of side effects from adjuvant chemotherapy was not increased in the elderly, except for one clinical trial reporting a higher rate of leukopenia (low white blood cell levels) in the elderly group. The analysis from this large sum of data confirms that elderly patients with colon cancer who are in otherwise good health have improved survival with adjuvant chemotherapy and tolerate this treatment regimen as well as younger patients.6

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage III colon cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of Stage III colon cancer include the following:

Adjuvant Chemotherapy

Research is ongoing to determine whether new drugs or drug combinations can improve outcomes of adjuvant chemotherapy. The combination of Xeloda and Eloxatin, for example, is being evaluated in a clinical trial of 1,864 patients with Stage III colon cancer.7

Advances in Surgery for Colon Cancer

Surgical removal of cancer remains an integral part of the treatment strategy for patients with Stage III colon cancer and many patients are cured with this treatment alone. Conventional surgical procedure involves the opening of the pelvis and/or abdomen to gain access to the large intestine. As with any surgery, there are risks associated with removing cancer, including infection, blood loss, and other possible complications of surgery.

Clinical trials have shown that a less invasive surgical technique, called laparoscopic surgery may be more tolerable than and similarly effective as conventional surgery. Laparoscopic surgery involves the placement of small probes into the area of surgery. The probes contain cameras and instruments for removing the cancer, which displays images onto large television screens in the operating room. The surgeon performs the surgery through the probes while watching his or her movements that are projected on a large screen. This type of procedure prevents the need for large surgical incisions, and may be associated with fewer complications, especially infections (abdominal infections, urinary tract infections and pneumonia). In addition, patients undergoing laparoscopic surgery generally experience less discomfort post-operatively and have a quicker recovery time (return to normal activities).

A study of 233 patients in the United Kingdom evaluated the long-term survival rates of open resection compared with laparoscopic resection.  The overall survival rates were similar in both groups, but traditional, open surgery was associated with a lower cumulative recurrence rate.8 The results mean that patients undergoing traditional surgery had a lower rate of cancer recurrence compared with the laparoscopic group.

An analysis of over 100 hospitals and 3,000 patients has shown that laparoscopic surgery is better tolerated in the short term compared with open abdominal surgery in the short term. Laparoscopic patients stayed fewer days in the hospital and had fewer infections.9

Another investigation of laparoscopic surgery for colon cancer involved 872 patients; approximately half of the patients underwent laparoscopic surgery to remove their cancer, and the other half underwent conventional surgery. The number of patients that experienced a recurrence of their cancer the number of patients that survived three years or more were approximately the same for both procedures. Patients who underwent laparoscopic surgery spent one less day in the hospital and required less pain medication compared to patients that underwent standard surgery.10

When choosing between open and laparoscopic abdominal surgery, patients and their doctors must weigh the potential short-term benefits of laparoscopic surgery with a possible small increase in cancer recurrence that may be associated with laparoscopic resection. Patients may choose based on their own health and the expertise and recommendations of their surgeon.

Targeted Therapy

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.

Avastin® (bevacizumab): Avastin is type of targeted therapy that slows or prevents the growth of new blood vessels, a process called angiogenesis. Cancer cells require food, oxygen, and proteins in order to grow and spread. New blood vessels are necessary to deliver these essential components of cellular growth. Avastin starves cancer cells by inhibiting angiogenesis. Avastin has been shown to improve outcomes among patients with metastatic colon  cancer,11 and is being studied among patients with earlier-stage colon cancer as well.

Erbitux® (cetuximab): Erbitux is a type of targeted therapy called a monoclonal antibody. It works by binding to a protein receptor located on many cancer cells called the epidermal growth factor receptor (EGFR). EGFR is involved in cellular growth and replication, and by targeting EGFR, the spread of cancer can be reduced or delayed.

Erbitux administered alone or with the chemotherapy drug  Camptosar® (irinotecan) has been shown to improve survival for patients with advanced, EGFR-positive colorectal cancer that has progressed on first-line therapy.12,13 A clinical trial of 2,000 patients will evaluate the role of Erbitux plus 5-FU/LV/Eloxatin  in Stage III colon cancer.14

Managing Side Effects

Techniques designed to prevent or control the side effects of cancer and its treatments are called supportive care. Side effects not only cause patients discomfort, but also may prevent the delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that treatment is delivered as planned and that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

References


1 Andre T, Boni C, Mounedji-Boudiaf, et al. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. New England Journal of Medicine. 2004;350:2343-2351.

2 Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. Journal of Clinical Oncology. 2007;25(16):2198-204.

3 Twelves C, Wong A, Nowacki M, et al. Capecitabine as Ajuvant Treatment for Stage III Colon Cancer. New England Journal of Medicine. 2005; 352:2696-2704.

4 Cassidy J, Douillard JY, Twelves C, et al. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes’ C colon cancer: the X-ACT trial. British Journal of Cancer. 2006;94(8):1122-9.

5 Twelves C, Wong A, Nowacki M, et al. Capecitabine as Ajuvant Treatment for Stage III Colon Cancer. New England Journal of Medicine. 2005; 352:2696-2704.

6 D Sargent, R Goldberg, J MacDonald, et al. Adjuvant Chemotherapy for Colon Cancer (CC) Is Beneficial Without Significantly Increased Toxicity in Elderly Patients (Pts): Results from a 3351 Pt Meta -Analysis. Proceedings from the 36th annual meeting of the American Society of Clinical Oncology. Blood. 2000;19: Abstract #933

7 Schmoll HJ, Cartwright R, Tabernero J, et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. Journal of Clinical Oncology. 2007;25(1):102-9.

8 Mirza MS, Longman RJ, Farrokhyar F, et al. Long-term outcomes for laparoscopic versus open resection of nonmetastatic colorectal cancer. Journal of Laparoendoscopic Advances in Surgical Technique. 2008;18(5):679-685.

9 Bilimoria KY, Bentrem DJ, Merkow RP, et al. Laparoscopic-assisted vs. Open Colectomy for Cancer: Comparison of Short-term Outcomes from 121 Hospitals. Journal of Gastrointestinal Surgery early online publication. June, 2008.

10 Nelson H, Sargent D, Wie H, et al. A Comparison of Laparoscopically Assisted and Open Colectomy for Colon Cancer. New England Journal of Medicine. 2004;350:2050-2059.

11Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine. 2004;350:2335-2342.

12 Cunningham D, Humblet Y, Siena S, et al. Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer. New England Journal of Medicine. 2004;351:337-345.

13 Hriesik C, Ramanathan R, Hughes S. Update for Surgeons: recent and noteworthy changes in therapeutic regimens for cancer of the colon and rectum. Journal of the American College of Surgeons. 2007; 205: 468-478.

14 Taieb J, Puig PL, Bedenne L. Cetuximab plus FOLFOX-4 for fully resected stage III colon carcinoma: scientific background and the ongoing PETACC-8 trial. Expert Reviews of Anticancer Therapy. 2008;8(2):183-9.

Copyright © 2014 Omni Health Media Colon Cancer Information Center. All Rights Reserved.


< Previous Page


Types Of Cancer
General Cancer Information
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer
Cervical Cancer
Colon Cancer
Esophageal Cancer
Gastric Cancer
Head and Neck Cancer
Hodgkin's Lymphoma
Leukemia
Liver Cancer
Lung Cancer
Melanoma
Mesothelioma
Multiple Myeloma
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Rectal Cancer
Renal Cancer
Sarcoma
Skin Cancer
Testicular Cancer
Thyroid Cancer
Uterine Cancer

Stage II Colon Cancer

Overview

Following surgical removal of colon cancer, the cancer is referred to as Stage II if the final pathology report shows that the cancer has penetrated the wall of the colon into the abdominal cavity, but does not invade any of the local lymph nodes and cannot be detected in other locations in the body.

Stage II adenocarcinoma of the colon is a common and curable cancer. Depending on features of the cancer, 60-75% of patients are cured without evidence of cancer recurrence following treatment with surgery alone. Stage II cancer can be further divided into two stages, Stage IIA and Stage IIB. In Stage IIA, the tumor has grown through the outermost layers of the colon but is confined to the colon. In Stage IIB, the tumor has grown through the colon wall and has extended to adjacent tissues or organs. In both stages, there are no lymph nodes containing tumor cells and no distant metastases.

Despite undergoing complete surgical removal of the cancer, 25-40% of patients with Stage II colon carcinoma experience recurrence of their cancer. Typically, cancer recurs because there are small amounts of cancer that had spread outside the colon and were not removed by surgery. These cancer cells cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the colon are referred to as micrometastases. The presence of micrometastases causes the relapses that follow surgical treatment. An effective treatment is needed to eliminate micrometastases and improve cure rates of Stage II cancer. Efforts are currently underway to find such a therapy.

The following is a general overview of treatment for Stage II colon cancer. Treatment may consist of surgery, radiation, chemotherapy and/or targeted therapy (drugs which act by a different mechanism than chemotherapy to target tumor cells). Multi-modality treatment, which is treatment using two or more techniques, is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

Adjuvant Chemotherapy

The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy, and/or targeted therapy. Adjuvant chemotherapy improves outcomes among patients with Stage III colon cancer, but the benefits among patients with Stage II colon cancer are less clear. A review of previously published clinical trials reported that adjuvant chemotherapy may improve disease-free survival, but does not appear to improve overall survival, among patients with Stage II colon cancer.1 Routine use of adjuvant chemotherapy is not recommended for patients with Stage II colon cancer, but it may be considered for some patients, particularly those whose cancers have high-risk features.2

Characteristics that may indicate a higher risk of recurrence include the following:3 4

  • High grade cells on pathologic exam
  • Less than 12 lymph nodes sampled during surgery
  • Perforation or obstruction of the colon due to cancer
  • Stage IIB tumors (tumor has extended beyond the wall of the colon)

The overall health of the patient must also be considered when weighing the risks and benefits of adjuvant therapy. Patients with fewer other health problems (such as diabetes, obesity or heart disease) will better tolerate adjuvant chemotherapy.

Oncotype DX Testing

A newer test that may help guide treatment decisions for patients with Stage II colon cancer is the Oncotype DX colon cancer test. This test—which is similar to a test that is commonly used for patients with early-stage breast cancer—is performed after surgery but before final decisions are made about adjuvant (post-surgery) therapy. The test estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue. Risk of recurrence can vary greatly among patients with Stage II colon cancer, and use of the Oncotype DX test in combination with other markers of risk may help to individualize treatment decisions.

Treatment of the Elderly

A large percentage of patients with colon cancer are 65 years or older. Sometimes elderly patients and/or their physicians may believe that believe that treatment will be more toxic for elderly patients than it is for their younger counterparts. Due to this perceived intolerability of therapy, elderly patients often do not receive optimal treatment.

To explore the risks and benefits of chemotherapy by age, researchers analyzed data from 7 separate clinical trials that were conducted to evaluate adjuvant chemotherapy in patients with Stage II or III colon cancer. Patients were divided into four age groups: 50 years and younger, 51 to 60 years, 61 to 70 years and 70 years and older. In these trials, patients received either surgery alone or surgery followed by adjuvant chemotherapy consisting of either fluorouracil plus leucovorin or fluorouracil plus levamisole. Five years following treatment, the overall survival rate was 71% for patients treated with adjuvant chemotherapy versus only 64% for those treated with surgery alone. There were no differences in survival rates between the age groups. The incidence of side effects from adjuvant chemotherapy was not increased in the elderly, except for one clinical trial reporting a higher rate of leukopenia (low white blood cell levels) in the elderly group. The analysis from this large sum of data confirms that elderly patients with colon cancer who are in otherwise good health tolerate chemotherapy as well as younger patients.5

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage II colon cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of Stage II colon cancer include the following:

New Adjuvant Chemotherapy

Several new chemotherapy and biological drugs demonstrate promising activity for the treatment of colon cancer. Clinical research is ongoing to develop new multi-drug treatment regimens that incorporate new anti-cancer therapies for use as adjuvant treatment. Eloxatin® (oxaliplatin) and Xeloda® (capecitabine) are chemotherapy drugs that have been recently approved for the treatment of Stage III colon cancer and may provide benefit in the adjuvant treatment of Stage II disease.

Eloxatin® (oxaliplatin): Eloxatin is a platinum-based chemotherapy drug that was approved for the treatment of advanced colon cancer in early 2004. In the treatment of patients with Stage II or Stage III colon cancer that had been completely removed with surgery, adjuvant treatment with Eloxatin®/5-FU/LV (FOLFOX) helped patients survive longer without cancer than 5FU/LV. This was a large trial that involved 2246 patients, half of which were treated with Eloxatin plus 5-FU/LV and the other half were treated with 5-FU/LV. The Stage II patients who received Eloxatin experienced fewer cancer-related events and approximately 87% were disease-free for 3 years or more, compared to 84% who did not receive Eloxatin.6 Eloxatin is now FDA-approved for the adjuvant treatment of Stage III colon cancer. Since doctors can prescribe medication for treatment of conditions other than that which they are approved, some patients with Stage II colon cancer may be able to receive treatment with Eloxatin.

Xeloda® (capecitabine): Xeloda is a form of the chemotherapy drug fluorouracil that is administered orally, as a pill, rather than into a vein. Intravenous (IV) drug administration is associated with more side effects than oral administration. Side effects of IV fluorouracil may include pain and infection at the injection site. Current research evaluating Xeloda in the treatment of various cancers indicates comparable efficacy to 5-FU in colorectal cancer with fewer side effects. In addition, oral administration is more convenient since it requires fewer clinic visits—patients receiving Xeloda will make a minimum of eight trips to their clinic, whereas those on 5-FU may go up to 30 times.7 Xeloda has been FDA-approved for the treatment of Stage III colon cancer and may also benefit patients with Stage II disease.

Advances in Surgery for Colon Cancer

Surgical removal of cancer remains an integral part of the treatment strategy for patients with Stage II colon cancer and many patients are cured with this treatment alone. Conventional surgery involves opening the pelvis and/or abdomen to gain access to the large intestine. As with any surgery, there are risks associated with removing cancer, including infection, blood loss, and other possible complications of surgery.

Clinical trials have shown that a less invasive surgical technique, called laparoscopic surgery, may be more tolerable than and similarly effective as conventional surgery. Laparoscopic surgery involves the placement of small probes into the area of surgery. The probes contain cameras and instruments for removing the cancer. The surgeon performs the surgery through the probes while watching his or her movements captured by the camera and projected on a large screen. This type of procedure prevents the need for large surgical incisions, and may be associated with fewer complications, especially infections (abdominal infections, urinary tract infections and pneumonia). In addition, patients undergoing laparoscopic surgery generally experience less discomfort post-operatively and have a quicker recovery time (return to normal activities).

A recent study of 233 patients in the United Kingdom evaluated the long-term survival rates of open resection compared with laparoscopic resection. The overall survival rates were similar in both groups, but traditional, open surgery was associated with a lower cumulative recurrence rate.8 The results mean that patients undergoing traditional surgery had a lower rate of cancer recurrence compared with the laparoscopic group.

An analysis of over 100 hospitals and 3,000 patients has shown that laparoscopic surgery is better tolerated in the short term compared with open abdominal surgery in the short term. Laparoscopic patients stayed fewer days in the hospital and had fewer infections.9

Another investigation of laparoscopic surgery for colon cancer involved 872 patients; approximately half of the patients underwent laparoscopic surgery to remove their cancer, and the other half underwent conventional surgery. The number of patients that experienced a recurrence of their cancer and the number of patients that survived three years or more were approximately the same for both procedures. Patients who underwent laparoscopic surgery spent one less day in the hospital and required less pain medication compared to patients that underwent standard surgery.10

When choosing between open and laparoscopic abdominal surgery, patients and their doctors must weigh the potential short-term benefits of laparoscopic surgery with a possible small increase in cancer recurrence that may be associated with laparoscopic resection. Patients may choose based on their own health and the expertise and recommendations of their surgeon.

Targeted Therapy

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.

Avastin® (bevacizumab): Avastin is type of targeted therapy that slows or prevents the growth of new blood vessels, a process called angiogenesis. Cancer cells require food, oxygen, and proteins in order to grow and spread. New blood vessels are necessary to deliver these essential components of cellular growth. Avastin starves cancer cells by inhibiting angiogenesis. Avastin has been shown to improve outcomes among patients with metastatic colon cancer,11 and is being studied among patients with earlier-stage colon cancer as well.

Erbitux® (cetuximab): Erbitux is a type of targeted therapy called a monoclonal antibody. It works by binding to a protein receptor located on many cancer cells called the epidermal growth factor receptor (EGFR). EGFR is involved in cellular growth and replication, and by targeting EGFR, the spread of cancer can be reduced or delayed.

Erbitux administered alone or with the chemotherapy drug Camptosar® (irinotecan) has been shown to improve survival for patients with advanced, EGFR-positive colorectal cancer that has progressed on first line therapy.12 13

Managing Side Effects

Techniques designed to prevent or control the side effects of cancer and its treatments are called supportive care. Side effects not only cause patients discomfort, but also may prevent the delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that treatment is delivered as planned and that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

References


1 Figuerdo A, Coombes ME, Mukherjee S. Adjuvant therapy for completely resected stage II colon cancer.Cochrane Database of Systematic Reviews. 2008;(3):CD005390.

2 Benson AB, Schrag D, Somerfield MR. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. Journal of Clinical Oncology. 2004;15:3408-19.

3 Benson A, Schrag D, Somerfield M, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. Journal of Clinical Oncology. 2004; 22: 3408-3419.

4 Figueredo A, Charette M, Maroun J, et al. Adjuvant therapy for stage II colon cancer: A systematic review from the Cancer Care Ontario Program in Evidence-based Care’s Gastrointestinal Cancer Disease Site Group. Journal of Clinical Oncology. 2004;22: 3395-3407.

5 D Sargent, R Goldberg, J MacDonald, et al. Adjuvant Chemotherapy for Colon Cancer (CC) Is Beneficial Without Significantly Increased Toxicity in Elderly Patients (Pts): Results from a 3351 Pt Meta -Analysis. Proceedings from the 36th annual meeting of the American Society of Clinical Oncology. Blood. 2000;19: Abstract #933.

6 Andre T, Boni C, Mounedji-Boudiaf, et al. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. New England Journal of Medicine. 2004;350:2343-2351.

7 Twelves C, Wong A, Nowacki M, et al. Capecitabine as Adjuvant Treatment for Stage III Colon Cancer.New England Journal of Medicine. 2005; 352:2696-2704.

8 Mirza MS, Longman RJ, Farrokhyar F, et al. Long-term outcomes for laparoscopic versus open resection of nonmetastatic colorectal cancer. Journal of Laparoendoscopic Advances in Surgical Technique 2008;18(5):679-685.

9 Bilimoria KY, Bentrem DJ, Merkow RP, et al. Laparoscopic-assisted vs. Open Colectomy for Cancer: Comparison of Short-term Outcomes from 121 Hospitals. Journal of Gastrointestinal Surgery [early online publication]. June, 2008.

10 Nelson H, Sargent D, Wie H, et al. A Comparison of Laparoscopically Assisted and Open Colectomy for Colon Cancer. New England Journal of Medicine 2004;350:2050-2059.

11 Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine. 2004;350:2335-2342.

12 Cunningham D, Humblet Y, Siena S, et al. Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer. New England Journal of Medicine 2004;351:337-345.

13 Hriesik C, Ramanathan R, Hughes S. Update for Surgeons: recent and noteworthy changes in therapeutic regimens for cancer of the colon and rectum. Journal of the American College of Surgeons2007; 205: 468-478.

Copyright © 2014 Omni Health Media Colon Cancer Information Center. All Rights Reserved.


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Types Of Cancer
General Cancer Information
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer
Cervical Cancer
Colon Cancer
Esophageal Cancer
Gastric Cancer
Head and Neck Cancer
Hodgkin's Lymphoma
Leukemia
Liver Cancer
Lung Cancer
Melanoma
Mesothelioma
Multiple Myeloma
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Rectal Cancer
Renal Cancer
Sarcoma
Skin Cancer
Testicular Cancer
Thyroid Cancer
Uterine Cancer

Stage I Colon Cancer

Overview

Following colon cancer surgery, the cancer is classified as a Stage I colon cancer if the final pathology report shows that the cancer is confined to the lining of the colon. Stage I cancer does not penetrate the wall of the colon into the abdominal cavity, has not spread to any adjacent organs or local lymph nodes and cannot be detected in other locations in the body.

Depending on features of the cancer under the microscope, Stage I colon cancer survival rates are high: approximately 90% of patients are cured with colorectal surgery alone and will not have evidence of cancer recurrence.

Despite undergoing surgical removal of the cancer, a minority of patients with Stage I colon cancer may experience recurrence of their cancer. It is important to realize that a few patients with Stage I disease already have small amounts of cancer that have spread outside the colon and were not removed by surgery. These cancer cells cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the colon are referred to as micrometastases. The presence of micrometastases causes the relapses that follow treatment with surgery alone. An effective treatment is needed to eliminate micrometastases in order to improve the cure rate achieved with surgical removal of the cancer. Efforts are currently underway to find such a therapy.

The following is a general overview of treatment for Stage I colon cancer. Treatment may consist of surgery with or without adjuvant (post-surgery) treatment. Multi-modality treatment, which is treatment using two or more techniques, is increasingly recognized as an important approach for increasing some patients’ chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Web site is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

Surgery

Surgery to remove the cancer is the primary treatment for Stage I colon cancer. In some cases, it’s possible to completely remove a cancerous colon polyp during colonoscopy. In other cases, colon cancer surgery may involve open surgery (which involves a single large incision) or laparoscopic surgery (which involves several small incisions).

Adjuvant Therapy

The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy and/or targeted therapy. Adjuvant chemotherapy is commonly used for patients with Stage III colon cancer and may also be used in selected patients with Stage II colon cancer. The goal of chemotherapy in these patients is to reduce the risk of cancer recurrence. Thus far, clinical trials have not been performed evaluating adjuvant treatment in patients with Stage I cancers because of the very high cure rate achieved with surgery alone.

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage I colon cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of Stage I colon cancer include the following:

Improvement in Predicting Need for Adjuvant Therapy: Undetectable areas of cancer outside the colon are referred to as micrometastases. The presence of micrometastases may cause the cancer to relapse following treatment with surgery alone, but physicians currently cannot predict which patients will relapse.

Adjuvant chemotherapy has been shown to decrease the risk of cancer recurrence in patients with Stage III colon cancer, but benefits in patients with Stage I cancer — who have a high rate of cure with surgery alone — have not been demonstrated. New methods of determining which patients with early-stage colon cancer are at highest risk of cancer recurrence may identify a subset of patients who could potentially benefit from adjuvant treatment. A test that is being used for some patients with Stage II colon cancer is the Oncotype DX colon cancer test. The test estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue.

Copyright © 2014 Omni Health Media Colon Cancer Information Center. All Rights Reserved.


< Previous Page


Types Of Cancer
General Cancer Information
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer
Cervical Cancer
Colon Cancer
Esophageal Cancer
Gastric Cancer
Head and Neck Cancer
Hodgkin's Lymphoma
Leukemia
Liver Cancer
Lung Cancer
Melanoma
Mesothelioma
Multiple Myeloma
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Rectal Cancer
Renal Cancer
Sarcoma
Skin Cancer
Testicular Cancer
Thyroid Cancer
Uterine Cancer

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