New Choices for Advanced Colon Cancer Patients

For roughly twenty years, the standard chemotherapy regimen for advanced colorectal cancer has consisted of the drugs 5-fluorouracil (5-FU) and leucovorine. [1] However, advances within the last few years have introduced a range of new and more effective treatment options. While much remains to be understood about the optimal combinations of these therapies and the specific patient populations most likely to benefit, patients with advanced colon cancer will have the opportunity to about double their expected survival time with these therapies.

In 2005, the American Cancer Society estimated that there will be 145,000 new colorectal cancer diagnoses in the U.S. and 56,000 colorectal cancer deaths. [2] In both men and women, colorectal cancer is the third most commonly diagnosed cancer—following prostate and lung cancer for men and breast and lung cancer for women. Small colon cancers that have been detected early or have not yet spread to lymph nodes or distant sites in the body can often be treated with surgery alone. But if your cancer has spread to nearby lymph nodes (stage III) or to distant sites such as the liver or lungs (stage IV), surgery alone does not typically remove all the cancer. In these cases, chemotherapy and newer targeted therapies become an important part of treatment.

Recent advances in colon cancer treatment include new chemotherapy drugs and new combinations of drugs, as well as "targeted therapies" that kill cancer cells with fewer side effects on normal tissue.

Stage IV Colon Cancer

With the use of newer treatment regimens, half of the patients diagnosed with stage IV colon cancer will survive for at least 20 months. This is twice as long as the median survival after treatment with 5-FU and leucovorin alone. 1 Newer therapies that make this substantial leap possible include the chemotherapy drugs Eloxatin™ (oxaliplatin) and Camptosar® (irinotecan), as well as the monoclonal antibodies Avastin™ (bevacizumab) and Erbitux™ (cetuximab).

For first-line therapy in stage IV patients, Eloxatin or Camptosar are given in combination with 5-FU and leucovorin. The combination with Eloxatin is known as FOLFOX, while the Camptosar combination is known as FOLFIRI. Both of these chemotherapy regimens result in longer survival and greater shrinkage of tumors when compared to treatment with 5-FU and leucovorin alone. 1 Eloxatin was approved for first-line therapy of stage IV colon cancer in January 2004, and Camptosar was approved in April 2000.

These new chemotherapy combinations are joined by advances in "targeted therapies". Avastin and Erbitux are monoclonal antibodies that were both approved in 2004. Antibodies are produced by your immune system to fight infection. Monoclonal antibodies use a similar approach, but are made in the lab and designed to fight cancer cells. Avastin targets and suppresses a growth factor in your body that stimulates development of new blood vessels. Without new blood vessels, tumors are not able to grow or spread. Erbitux suppresses a growth factor that plays a role in the growth and survival of cancer cells. By targeting cancer cells and sparing normal tissue, these therapies produce fewer side effects than most chemotherapy drugs.

Avastin is now often used for first-line therapy of stage IV colon cancer because it improves survival compared to treatment with chemotherapy alone. Erbitux is approved as a second-line therapy (therapy given to patients whose cancer progresses after first-line treatment) and is typically given with the chemotherapy drug Camptosar, or alone for patients who cannot tolerate Camptosar. The role of Erbitux as a first-line therapy is currently being evaluated.

Stage III Colon Cancer

Two notable advances in the treatment of stage III colon cancer emerged this past year: Drugs initially FDA approved only for use in stage IV colon cancer were also found to be safe and effective when used in stage III patients.

Eloxatin, part of the FOLFOX chemotherapy regimen, was approved for use in patients with stage III cancer in November 2004. In the clinical trial that prompted FDA approval, stage III colon cancer patients who received adjuvant treatment with FOLFOX survived longer with no signs of recurrence than patients treated with adjuvant 5-FU and leucovorin.

In addition to Eloxatin, Xeloda® (capecitabine) was approved for use in stage III patients in June 2005. Xeloda is an oral chemotherapy drug that is converted to 5-FU in the body. As an oral medication, Xeloda can be more convenient to take than intravenous chemotherapy drugs.

Our Understanding Evolves

The evidence about the most effective uses of these newer therapies continues to evolve. According to a review of colon cancer treatments published in the Journal of Clinical Oncology, "…our options currently outstrip our evidence." However, while researchers continue to study the optimal combinations of these new therapeutics, and the most appropriate patient populations for each, patients can be assured that the availability of these new treatment approaches has improved outcomes for patients with stage III and stage IV colon cancer.

References:

1) Kelly H, Goldberg RM. Systemic therapy for metastatic colorectal cancer: current options, current evidence. Journal of Clinical Oncology. 2005;23:4553-4560.

2) American Cancer Society. Cancer Facts and Figures 2005. http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf (accessed 8/22/2005).

Tags: Colon Cancer