Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Colon and Rectal Cancer Home Page 2 NCI's gateway for information about colon and rectal cancer. Highlights from ASCO 2003 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2003 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Colorectal cancer, FOLFOX, oxaliplatin. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

The chemotherapy regimen known as FOLFOX – oxaliplatin plus fluorouracil (5-FU) plus leucovorin – produced higher response rates and a significant delay in tumor progression in patients with metastatic colorectal cancer, compared to other therapy.

Source

American Society of Clinical Oncology (ASCO) annual meeting, Chicago, June 1, 2003. The data were also published in the June 1, 2003, issue of the Journal of Clinical Oncology; see the journal abstract.

Background

Early results from this trial – called EFC 4584 – led to U.S. Food and Drug Administration (FDA) approval of oxaliplatin as a treatment for patients with advanced colorectal cancer that had progressed after chemotherapy (second-line therapy). These final results substantiate the earlier data and provide more details than have been available up to now, including survival data.

(A separate trial also presented at the 2003 ASCO confirms earlier data on the superiority of the FOLFOX regimen as initial – “first line” – therapy for advanced colorectal cancer. Mature data from the N9741 trial, an intergroup trial led by the North Central Cancer Treatment Group, showed conclusively that FOLFOX was more effective than two other combinations in these patients, increasing both response rate and survival, while lowering toxicity. The North Central Cancer Treatment Group is an NCI-sponsored clinical trials cooperative group. N9741 was sponsored by NCI in partnership with the maker of oxaliplatin, Sanofi-Synthelabo.)

The Study

The 821 patients in the multicenter EFC 4584 trial, led by Mace L. Rothenberg, M.D., at the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., had metastatic colorectal cancer that had first been treated with the standard therapy of irinotecan, 5-FU, and leucovorin, known as IFL (also known as the Saltz regimen). They were randomly divided into three groups; one group received 5-FU and leucovorin, one received oxaliplatin alone, and one received the FOLFOX combination.

Results

About 9 percent of patients responded to the FOLFOX regimen compared to about 1 percent for the other two regimens. The delay in tumor progression was 4.9 months for patients receiving FOLFOX and 2.6 months for those receiving 5-FU and leucovorin. Oxaliplatin as a single agent produced results comparable to 5-FU and leucovorin. These results “were highly statistically significant,” said Rothenberg.

Substantial side effects were more frequent among patients receiving FOLFOX. These patients were more likely to experience nausea, diarrhea, neuropathy, and low white blood cell and platelet counts compared to those who received either of the other two therapies.

Nonetheless, concluded the investigators, these results mean that FOLFOX offers a useful “second line” therapy option to patients whose treatment with IFL fails to stop the disease.

Limitations

Although the response rates and time to tumor progression were superior for FOLFOX as a second-line therapy, the trial was not able to demonstrate an overall survival advantage for the regimen.

Glossary Terms

A drug used to treat symptoms of cancer of the colon, breast, stomach, and pancreas. It is also used in a cream to treat certain skin conditions. 5-FU stops cells from making DNA and it may kill cancer cells. It is a type of antimetabolite. Also called 5-fluorouracil and fluorouracil.

Treatment with drugs that kill cancer cells.

The active ingredient in a drug used alone or in combination with other drugs to treat colon cancer or rectal cancer that has spread to other parts of the body or has come back after treatment with fluorouracil. It is also being studied in the treatment of other types of cancer. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of topoisomerase inhibitor and a type of camptothecin analog.

The active ingredient in a drug used to lessen the toxic effects of substances that block the action of folic acid, especially the anticancer drug methotrexate. Leucovorin is used to treat some types of anemia and is also used together with fluorouracil to treat colorectal cancer. It is also being studied in the treatment of other types of cancer and other conditions. Leucovorin is a form of folic acid. It is a type of chemoprotective agent and a type of chemosensitizing agent. Also called folinic acid.

A drug used together with other drugs to treat colorectal cancer that is advanced or has come back. It is also being studied in the treatment of other types of cancer. Oxaliplatin attaches to DNA in cells and may kill cancer cells. It is a type of platinum compound. Also called Eloxatin.

A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

The percentage of patients whose cancer shrinks or disappears after treatment.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.