Overview

When  colon cancer has been detected or has returned following an initial treatment with surgery, radiation therapy, and/or chemotherapy it is said to be recurrent or relapsed.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase the duration of survival, or ultimately improve the chance of cure. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of recurrent colon cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. In addition to this treatment overview, the Cancer Treatment News web site feature presents the results of the actual clinical trials that determine the standard treatments of colon cancer and new treatment strategies as they have been discovered and applied by cancer physicians around the world.

All new treatments are evaluated in clinical trials. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Remember, this web site information is intended to help educate you about  your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Patients experiencing a recurrence of colon cancer have been perceived to have few treatment options. Certain patients, however, can still be cured of their cancer, and others derive meaningful benefit from additional treatment. Patients with recurrent colon cancer can be broadly divided into two groups, those with recurrent cancer that can be surgically removed with curative intent, and those with more widespread cancer.

Treatment of Metastatic Colon Cancer to One Site

Colon cancer may metastasize to the liver, lung, or other locations. 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 site of metastasis. The most common location of metastasis with colon cancer is the liver. Highly selected patients with isolated areas of colon cancer can be cured if the primary cancer in the colon and the isolated area of cancer outside the colon can be surgically removed.  Several clinical trials have reported that isolated areas of colon cancer in the liver or lungs can be removed surgically and cured in approximately 25% of circumstances. Surgical removal of cancer can be accomplished with acceptable toxicity, even in community cancer centers, with mortality rates of approximately 2%.

Liver-Directed Therapies

For Patients with disease confined to the liver who are not surgical candidates, several other liver-directed treatments approaches have been developed. The goal of liver-directed therapies are to inject chemotherapy directly into the blood supply of the liver thereby delivering chemotherapy directly to the cancer and/or block the flow of blood to the liver to further “starve” the cancer cells by preventing the necessary blood flow.

Chemotherapy injected directly into the hepatic artery [hepatic artery infusion (HAI)]  has the potential advantage of delivering higher doses of anti-cancer therapy directly to the cancer cells in the liver while avoiding the side effects of chemotherapy delivered systemically. Techniques that interrupt blood flow to the cancer cells in the liver can simply block (chemoemobilization) or closes the hepatic artery (hepatic artery ligation). These liver-directed treatment approaches are all highly specialized procedures and when performed by experienced individuals in highly selected patients have produced some encouraging treatment results. In order for these procedures to become widely used, the risk and benefit of liver-directed therapies must outweigh the risk and benefit from standard surgical removal of isolated liver lesions and systemic chemotherapy. 

Hepatic Artery Infusion: Hepatic artery infusion has been the most widely evaluated of the liver-directed treatment strategies. The most commonly used chemotherapeutic agent infused into the hepatic artery is FUdR. A clinical study in patients with cancer confined to the liver compared hepatic artery infusion with FUdR to no additional treatment. The study demonstrated that patients treated with hepatic artery infusion survived on average 13.5 months compared to 7.5 months for patients receiving no additional treatment. 

Hepatic Artery Infusion and Systemic Chemotherapy: When rectal cancer has spread to the liver, it is likely that cancer may exist elsewhere in the body; therefore, many doctors have advocated giving systemic chemotherapy over hepatic artery infusion chemotherapy directed exclusively to the cancer cells in the liver. Several clinical studies have been performed in patients with cancer metastatic to the liver which compare hepatic artery infusion with FUdR to treatment with systemic 5-fluorouracil-based chemotherapy. An analysis of all these trials together has demonstrated that hepatic artery infusion produces a higher remission rate than systemic chemotherapy; however, the average overall survival is not significantly improved. Patients treated with hepatic artery infusion lived on average 16 months compared to 12 months for patients treated with systemic 5-fluorouracil chemotherapy.

One clinical trial has compared the effectiveness of hepatic artery infusion and systemic infusion of chemotherapy administered into a vein versus systemic infusion chemotherapy alone. Physicians randomly allocated 156 patients with colorectal cancer to two groups. One group received 6 cycles of chemotherapy into the hepatic artery and systemic chemotherapy while the other group only received systemic chemotherapy. The survival was 86% at 2 years for patients receiving treatment with hepatic artery infusion and systemic chemotherapy and 72% for patients receiving systemic chemotherapy alone. The average survival was 72 months for the combined treatment and 59  months for systemic chemotherapy treatment alone. Only 10% of patients receiving combined treatment develop a cancer recurrence compared to 60% of patients receiving the systemic chemotherapy treatment alone. The combined therapy did not lead to an increased mortality.

In summary, for patients with colon cancer isolated to the liver who are unable to undergo surgical removal of the cancer, hepatic artery infusion improves response rates and prolongs survival when compared to no treatment and may produce a minor survival advantage compared to patients treated with systemic 5-fluorouracil chemotherapy.

Treatment of Recurrent Colon Cancer to Multiple Sites

While some patients have a single site of cancer that can be treated with curative intent, the majority of patients have unresectable or widespread disease.  Historically, these patients have been considered incurable and were offered treatment with chemotherapy for the purpose of prolonging their survival and alleviating symptoms from progressive cancer. 

Single-agent fluorouracil chemotherapy with or without leucovorin has been the standard treatment approach for over 30 years. Treatment with fluorouracil chemotherapy regimens induce a remission or shrinkage of the cancer in 15%-45% of patients, and the average patient survives approximately 1 year from treatment.  Continuous-infusion fluorouracil appears to have less toxicity and provide more benefit than bolus fluorouracil therapy. The biologic agent interferon has also been added to fluorouracil and leucovorin. The addition of interferon did not prolong patient’s survival and may have diminished patients’ quality of life. Patients electing to receive treatment with fluorouracil should discuss the potential side effects from treatment as they vary considerably across the many different fluorouracil chemotherapy regimens.

Recently, several newer chemotherapeutic drugs have demonstrated a substantial ability to kill colon cancer cells in patients with recurrent cancer. Developing and exploring single or multi-agent chemotherapy agents as a treatment approach for patients with widespread colon cancer is an area of active investigation. In particular, the chemotherapy drug Camptosar® and oxaliplatin are known to be active drugs for the treatment of patients with colorectal carcinoma.

The results of a clinical trial directly comparing Camptosar® to the best supportive care available in patients with colorectal cancer that no longer responded to chemotherapy with fluorouracil have been reported. In this direct comparison, patients receiving the Camptosar® treatment were 2.6 times more likely to be alive after 1 year of treatment. Moreover, patients receiving Camptosar® felt better and had an improved quality of life. Camptosar® is now considered a standard treatment for patients with colorectal cancer.

Strategies to Improve Treatment of Recurrent Colon Cancer

While some progress has been made in the treatment of colon cancer, the majority of patients still succumb to cancer, and better treatment strategies are clearly needed. Future progress in the treatment of colon cancer will result from patients continuing to participate in appropriate clinical trials. Areas of active exploration to improve  the treatment of colon cancer include the following:

New Chemotherapy Regimens: Several new chemotherapy drugs show promising activity for the treatment of colon cancer.  Camptosar® and Oxaliplatin are being evaluated in clinical trials in combination with other chemotherapy drugs and at other doses and schedules of administration with the hope that this will further improve the treatment of patients with colorectal cancer. Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research.

Angiogenesis: Angiogenesis, a scientific term for the formation of blood vessels, is crucial to the development of cancer and other diseases that require the development of new blood vessels to supply them with essential nutrients for growth. Angiogenesis-dependent diseases form new blood vessels by sending out certain proteins, such as VEGF (vascular endothelial growth factor) that cause endothelial cells within existing nearby blood vessels to proliferate and migrate secreting enzymes called matrix metaproteinases or MMP’s, which create an opening in the surrounding matrix, enabling these endothelial cells to form new blood vessels that reach out to the disease.

A substance in the body, called vascular endothelial growth factor (VEGF), plays a crucial role in the progression of cancer by stimulating the new growth of blood vessels. In essence, VEGF stimulates the body to provide a blood supply for a newly developing cancer. Researchers have developed a type of antibody, a recombinant humanized monoclonal antibody called rhuMAb VEGF, that inhibits the effects of VEGF in the body. This monoclonal antibody has now been studied in persons with metastatic colorectal cancer.

Researchers assigned 104 persons with metastatic colorectal cancer to receive treatment with either fluorouracil and leucovorin alone or fluorouracil, leucovorin, and rhuMAb VEGF. Twenty-one percent of those receiving the chemotherapy alone had a response to treatment, compared with 34% of those who also received the rhuMAb VEGF. The average time it took for the cancer to begin growing again (called time to progression) was 5.4 months in those receiving the chemotherapy alone and 6.8 to 7.3 months in those also receiving the rhuMAb VEGF. RhuMAb VEGF and other anti-angiogenesis components are being evaluated alone or in combination with chemotherapy. 

Liver-Directed Therapies: Continued development and refinement of hepatic artery infusion, chemoembolization, and other liver-directed therapies is ongoing. For patients with liver dominant disease, these strategies are being utilized to shrink the cancer and increase the number of patients eligible for surgical removal of their cancer 

Biological Modifier Therapy: Biologic response modifiers are naturally occurring or synthesized substances that direct, facilitate, or enhance your body’s normal immune defenses. Biologic response modifiers include interferons, interleukins, vaccines and monoclonal antibodies. In an attempt to improve survival rates these and other agents are being tested alone or in combination with chemotherapy in clinical trials.

Monoclonal Antibodies: Another approach is to deliver additional treatment directed specifically to the cancer cells and avoid harming the normal cells. Monoclonal antibodies are a treatment that can locate cancer cells and kill them directly. Monoclonal antibodies are being evaluated alone or  in combination with chemotherapy to determine whether they can improve cure rates. The 17-IA monoclonal antibody has been shown to improve survival in patients with colorectal cancer in Germany. Although not available in the United States, clinical trials are ongoing  throughout the world to further evaluate the 17-IA monoclonal antibody.

Vaccines: The purpose of a vaccine is to help the patients immune system destroy the cancer by activating the patients immune cells against the cancer. Vaccines are made from a variety of substances that often include the actual cancer cells removed from the patient. A difficulty in preparing vaccines is that the patients cancer cells must be processed immediately following surgery. Patients and their surgeon must therefore prepare in advance to ensure the removed cancer cells can be handled properly for vaccine preparation. Vaccines have already been shown to improve the survival of certain patients with colorectal cancer and continue to be evaluated in clinical trials.

Phase I 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 anti-cancer activity in patients.

Oral Chemotherapy Agents: Several new chemotherapy agents are being developed that can be taken orally. The most common are the fluoropyrimidines, which may provide the same or greater benefit as intravenous fluorouracil without requiring intravenous administration.

USED WITH PERMISSION OF CANCERCONSULTANTS.COMcopyright® 1998, last updated 7/00, CancerConsultants.com – All Rights Reserved.

“The information contained above is  general in nature and is not intended as a guide to self-medication by consumers or meant to substitute for advice provided by your own physician or other medical professional. The reader is advised to consult with a physician or other medical professional and to check product information (including packaging inserts) for changes and new information regarding dosage, precautions, and contra indication before administering any drug, herb, supplement, compound, therapy or treatment discussed herein. Neither the editors nor the publisher accepts any responsibility for the accuracy of the information or consequences from the use or misuse of the information contained herein.”

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