Colon cancer is one of the most common cancers—about 500,000 people in the world die of it annually. Researchers at the Memorial Sloan-Kettering Cancer Center tested new dosing levels of two drugs that are usually administered separately. Previous tests have indicated that 5-FU and raltitrexed work better when combined, and this study aimed to establish the highest level of dosing possible for the drugs without reaching toxicity.

What the researchers wanted to know: What is the maximum amount of raltitrexed and 5-FU that can be given to patients with advanced colorectal cancer and appendiceal adenocarcinoma, a type of gastrointestinal cancer?

What they did: Researches recruited 71 patients with serious colorectal cancer and appendiceal adenocarcinoma. Participants could not have had recent surgery or serious infections. The medicines were injected into the patients once every three weeks. Researchers studied what happened to patients as they increased the dosages of the two medicines. In the first stage, the 5-FU dose remained constant while the raltitrexed dose was increased in small increments up to the dose recommended when raltitrexed is given alone. In the second stage, raltitrexed was fixed at the recommended single dose and 5-FU was increased in increments until at least two out of six patients experienced fever and a persistent drop in white blood cell count (known as dose limiting toxicity). In the third stage, patients were given a dose of 5-FU just below the toxic level and raltitrexed was increased in increments until the combination was too toxic in at least two of six patients - the level just below that was designated the maximum tolerated dose. Patients underwent physical examinations within a week before treatment, on each day of injections, and three weeks after the final dose of medication. The researchers measured each patient's tumor within three weeks of starting the treatment and every nine weeks during treatment using CAT scans and X-rays.

What they found: Nine percent of the 68 patients who could be evaluated experienced significant tumor shrinkage. The disease did not progress in 43 percent of participants. Researchers found that when raltitrexed was administered along with 5-FU, they could give patients more raltitrexed than when it's given alone. They say that the results of the study are positive, but that more clinical tests need to be performed.

What this means to you: Doctors are making progress in treating colorectal cancer. Raltitrexed appears to work better in combination with 5-FU. However, this method of treatment is still only in a phase I trial; more clinical trials are necessary before it can be approved.

Caveats: The worst toxic reactions to the drugs occurred in participants who had undergone significant treatment before entering the study. Researchers suggest that patients who have weak bone marrow should not use this treatment. This is only a phase I study (to evaluate drug toxicity and dosage). More extensive studies will be needed to evaluate this drug combination.

Find out more: Colorectal Cancer Network: http://www.colorectal-cancer.net

Read the article: Schwartz, Gary K., et al. "Phase I Trial of Sequential Raltitrexed Followed by Bolus 5-Flourouracil in Patients with Advanced Colorectal Cancer." Anti-Cancer Drugs. 2004, Vol. 15, No. 3, pp. 219-227.