Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Head and Neck Cancer Home Page 2 NCI's gateway for information about head and neck cancer. Highlights from ASCO 2004 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2004 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Head and neck cancer, cetuximab (Erbitux®), epidermal growth factor receptor. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

Compared to radiation alone, cetuximab plus radiation therapy can nearly double the median survival in patients with a certain kind of head and neck cancer that has not spread to other parts of the body. However, further research is needed to know whether cetuximab plus radiation is more effective than the current standard of care (chemoradiotherapy using the drug cisplatin).

Source

The New England Journal of Medicine, Feb. 9, 2006 (see the journal abstract).
(N Engl J Med. 2006 Feb 9;354(6):567-578)

Background

Initial treatment options for patients with advanced head and neck cancer include radiation therapy, chemotherapy combined with radiation treatment (called chemoradiotherapy), or surgery followed by radiation and/or chemotherapy. The current standard of care for such patients is chemoradiotherapy using one of the platinum drugs, such as cisplatin.

Severe mucositis often develops as a result of such treatment, a condition that can make it difficult to eat without use of a gastric tube. Researchers are trying to find effective treatments that aren't as toxic.

Many head and neck cancer cells overexpress (make too much of) a protein called the epidermal growth factor receptor (EGFR), which may help cancer cells to grow more aggressively. Cetuximab is a potentially less toxic targeted therapy - a monoclonal antibody that specifically attaches to and blocks EGFRs. Early studies suggested that treatment with cetuximab might boost the effectiveness of radiation therapy in patients with head and neck cancer.

The Study

Between 1999 and 2002, a total of 424 patients with stage III or IV head and neck cancer enrolled in this phase III trial at multiple locations in the United States and Europe. All patients had tumors in their tonsils, tongue, or voicebox that may have involved lymph nodes, but had not spread to other parts of the body.

Patients were randomly assigned to receive either radiation therapy alone (213) or radiation plus weekly cetuximab (211). Doctors treated the patients with one of three radiation therapy regimens, depending on each patient's disease characteristics. The overall radiation dose was about the same for all three regimens, but they differed in terms of fractionation.

All patients were followed up for a median of just over three years. The study’s principal investigator was James A. Bonner, M.D., of the University of Alabama at Birmingham. (See the protocol summary ⁵.)

The trial's findings were originally presented at the 2004 annual meeting of the American Society of Clinical Oncology.

Results

Median survival for patients treated with cetuximab was 49 months, compared with 29.3 months for patients who received radiation therapy alone. Fifty-five percent of the cetuximab-treated patients survived for three years, compared with 45 percent of those in the radiation-only group.

The combined treatment also did better in keeping cancer from progressing from where it was at the start of the trial (called "locoregional control"). The median duration of locoregional control was 24.4 months with the combined therapy and 14.9 months for radiation alone.

However, at the one-year and two-year marks, both groups sufferered distant metastases at about the same rate.

All in all, patients on the combined therapy saw their risk of death cut by 26 percent compared to the radiation-only group.

As for severe mucositis (grades 3 - 5), patients in both groups suffered from this side effect in roughly equal amounts: 52 percent of the radiation-only group and 56 percent of the cetuximab combination group.

Comments

“It is particularly encouraging that the increase in survival achieved with cetuximab was attained with no worsening of radiation-induced adverse effects,” said Bonner. Patients treated with cetuximab suffered more frequently from a skin rash on the face and body, but this did not appear to reduce the effectiveness of treatment.

Limitations

While the gain in survival without an increase in toxicity is notable, the results of this trial "should be examined in the context of the current standards of care for patients with head and neck cancer," write Marshall R. Posner, M.D., and Lori J. Wirth, M.D., of the Dana-Farber Cancer Institute in Boston, Mass. in an accompanying editorial.

The trial did not compare the cetuximab combination to a platinum-based chemoradiotherapy treatment, as is currently the standard. Also, they note, the trial did not administer the same radiation regimens to all patients, which complicates how the results should be interpreted.

In addition, the survival benefit was not the same across all types of head and neck cancer. "The benefit of cetuximab in terms of survival was evident for oropharyngeal cancer, the diagnosis in more than half the patients," write Posner and Wirth. "In contrast, the use of the antibody did not improve the survival among patients with hypopharyngeal or laryngeal cancer."

Finally, they write, "oncologists should keep in mind that all studies of platinium-based chemoradiotherapy have shown greater improvement in patients than [this trial] found with cetuximab....At present, for patients who can tolerate it, chemoradiotherapy with cisplatin remains the standard of care."

Glossary Terms

A monoclonal antibody used to treat certain types of head and neck cancer, and colorectal cancer that has spread to other parts of the body. It is also being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to cancer cells. Cetuximab binds to the epidermal growth factor receptor (EGFR), which is found on the surface of some types of cancer cells. Also called Erbitux.

Treatment that combines chemotherapy with radiation therapy. Also called chemoradiation.

A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent. Also called Platinol.

The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also called EGFR, ErbB1, and HER1.

Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days.

Cancer that forms in tissues of the hypopharynx (the bottom part of the throat). The most common type is squamous cell carcinoma (cancer that begins in flat cells lining the hypopharynx).

Cancer that forms in tissues of the larynx (area of the throat that contains the vocal cords and is used for breathing, swallowing, and talking). Most laryngeal cancers are squamous cell carcinomas (cancer that begins in flat cells lining the larynx).

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

The time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is. Also called median overall survival and median survival.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

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 complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth.

Cancer that forms in tissues of the oropharynx (the part of the throat at the back of the mouth, including the soft palate, the base of the tongue, and the tonsils). Most oropharyngeal cancers are squamous cell carcinomas (cancer that begins in flat cells lining the oropharynx).

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

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.

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