According to a recent article published in the journal

Cancer, evidence suggests that patients with colorectal cancer that has spread to the liver and cannot be surgically removed may benefit from 5-FU (5-fluorouracil) based combination chemotherapy delivered directly to the liver.

The liver is the largest organ in the body and is responsible for over 500 functions, including the secretion of glucose, proteins, vitamins and fats; the production of bile; the processing of hemoglobin and the detoxification of numerous substances. The liver is a common place of metastasis (spread) of certain types of cancer, particularly colon cancer. Research is ongoing to determine effective treatment strategies in the treatment of liver (hepatic) metastasis that has spread from colon cancer. Surgical removal of liver metastases produces high survival rates. However, some liver metastases cannot be surgically removed (non-resectable) either due to size or location of the cancer. Treatment of non-resectable colorectal liver metastases (CRLM) continues to frustrate physicians and researchers. Consequently, research is ongoing to determine the best chemotherapy drug combinations and the most effective delivery for the treatment of non-resectable CRLM.

One novel delivery strategy used in some patients with liver metastasis involves the administration of chemotherapy drugs directly into the main artery (hepatic artery) that constantly delivers blood to the liver. Hepatic arterial infusion (HAI) delivery may augment the anti-cancer effects of chemotherapy to the liver beyond the effects offered by systemic (full body) delivery through a few mechanisms: 1) the chemotherapy agent does not become diluted by mixing with the rest of the blood from the body prior to reaching the cancer, 2) the chemotherapy agent is not broken down in the body through biochemical processes prior to reaching the cancer, 3) larger amounts of the chemotherapy agent can reach the cancer with fewer associated systemic side effects.

Determining the best chemotherapy combinations with the most tolerable side effects is also an ongoing study for researchers. Systemic delivery of 5-FUDR (5-fluorodeoxyuridine) chemotherapy regimens has proven the efficacy of 5-FUDR. However, HAI delivery of 5-FUDR has proven to cause severe side effects and may cause sclerosing cholangitis (SC), which is an inflammation of bile ducts that leads to scar tissue, cirrhosis and impaired function of the liver. Consequently, researchers are looking at other chemotherapy drugs like 5-FU that may be tolerated by HAI and be as effective as 5-FUDR.

Researchers in Germany recently conducted a clinical trial to determine the efficacy of 5-FU based combination chemotherapy delivered by HAI in patients with non-resectable CRLM. Sixty-three patients were treated with the chemotherapy agents mitoxantrone, 5-FU, folinic acid, and mitomycin C by HAI through a catheter implanted by surgery into the hepatic artery. Patients received between 2 and 11 HAI cycles. Of the 63 patients, 54% had a partial or complete disappearance of CRLM, 41.3% had no change, and 4.8% had progressive disease. The average survival time from the start of HAI treatment was 23.7 months and 7 patients lived longer than 40 months. No patient died from treatment complications or developed SC. However, 2 patients had to stop therapy and 22 patients required brief hospitalization from the side effects of the therapy.

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These results are promising yet require more research for the use of 5-FU or newer chemotherapy delivered by HAI in the treatment of non-resectable CRLM. The advantages of systemic versus regional therapy are still debatable and further examination of the best chemotherapy combinations and delivery are warranted.

Patients with CRLM may wish to speak with their physician about the risks and benefits of participating in a clinical trial evaluating HAI therapy or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (

cancer.gov) and

www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (

Cancer, Vol 92, No 11, pp 2746-2753, 2001)

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