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.

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