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. Bevacizumab (Avastin) for Treatment of Solid Tumor 3 A fact sheet about bevacizumab (Avastin™), the first U.S. Food and Drug Administration (FDA)-approved biological therapy designed to inhibit the formation of new blood vessels to tumors. Highlights from ASCO 2005 4 A collection of links to material summarizing some of the important clinical trial results announced at the 2005 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Colorectal cancer, bevacizumab (Avastin®), FOLFOX, targeted therapy, chemotherapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁵.)

Summary

Patients with advanced colorectal cancer lived longer and went longer without disease progression when their FOLFOX chemotherapy regimen was supplemented with bevacizumab. Those who had FOLFOX alone, however, experienced less serious side effects. Bevacizumab alone does not produce results comparable to either.

Source

American Society of Clinical Oncology (ASCO) annual meeting. Orlando, May 14, 2005. Final results subsequently published in the April 20, 2007, Journal of Clinical Oncology (see the journal abstract).

Background

Bevacizumab (Avastin®) is a monoclonal antibody that may slow the growth of blood vessels that help keep tumors alive. It is an example of a targeted therapy, which attacks cancer cells while leaving most normal cells alone.

Based on its effectiveness in large trials, bevacizumab was approved by the U.S. Food and Drug Administration in 2004 as initial ( first-line) therapy for advanced colorectal cancer. These and other studies, however, showed that patients experienced some serious, though uncommon, side effects, including holes (perforations) in the colon or bowel, infection, and bleeding from the lungs or other organs.

One second-line chemotherapy drug used for patients whose colorectal cancer has returned is oxaliplatin (Eloxatin™), which slows the growth of rapidly dividing cells. A combination chemotherapy treatment that includes oxaliplatin is called FOLFOX4 – it consists of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin.

The Study

The current study is the first large randomized clinical trial to explore the role of bevacizumab in patients who had previously received treatment for advanced colorectal cancer. Researchers randomly assigned patients to one of three groups: one group was treated with bevacizumab alone; another group with FOLFOX4 alone; and the third group with FOLFOX4 plus bevacizumab.

All of the patients had been previously treated, though none with bevacizumab. Researchers enrolled 829 patients between November 2001 and April 2003, and followed the patients for a median of 28 months.

The study’s lead author is Bruce Giantonio, M.D. from the University of Pennsylvania in Philadelphia (see the protocol summary ⁶).

Results

Patients receiving the combination of bevacizumab and FOLFOX4 survived for an average of 12.9 months, which was 2.1 months longer than those receiving FOLFOX4 only. Patients receiving bevacizumab-only had clearly inferior results than either of the other two groups, and that part of the study was stopped early.

Patients in the bevacizumab plus FOLFOX4 group also did better in terms of disease progression, with an average delay of 7.2 months compared to 4.6 months in the FOLFOX4-only group, an advantage of 2.6 months.

Patients receiving FOLFOX4 only had fewer complications and side effects than those receiving bevacizumab in the combined treatment group; specifically, bleeding, high blood pressure, numbness, and vomiting.

Comments

In Giantonio’s opinion, “the side effects experienced in the combined treatment group, while greater than with FOLFOX alone, were not serious enough to offset the advantage in survival and disease-free progression.” Bowel perforations, for example, occurred in only six patients: three in the combination treatment group and three in the bevacizumab-only group.

Giantonio notes that bevacizumab’s effectiveness in colorectal cancer is probably related to its ability to interfere with the vascular endothelial growth factor (VEGF), which influences the growth of blood vessels (angiogenesis) that help to keep tumors alive.

The drug is “a potent mediator of angiogenesis, and in colorectal cancer we know that 40 to 60 percent of tumors . . . express VEGF, which is associated with recurrence,” said Giantonio.

Glossary Terms

A drug used to treat several types of cancer, including certain types of colorectal, lung, breast, and kidney cancers and glioblastoma. It is also being studied in the treatment of other types of cancer. Bevacizumab binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called Avastin.

Treatment with drugs that kill cancer cells.

Initial treatment used to reduce a cancer. First-line therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called induction therapy, primary therapy, and primary treatment.

A statistics term. The middle value in a set of measurements.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

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 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.

Treatment that is given when initial treatment (first-line therapy) doesn’t work, or stops working.

A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treatments.