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Key Words

Head and neck cancer, chemotherapy, radiation. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

Patients with head and neck cancer who were treated with chemotherapy in addition to radiation after surgery had fewer recurrences of disease and longer disease-free survival than patients who were treated with radiation alone after surgery, two randomized clinical trials have found. However, patients who received chemotherapy had higher rates of severe side effects than those who did not. Only one of the two studies found that patients lived longer if they received chemotherapy.

Source

New England Journal of Medicine, May 6, 2004.

Background

Patients with advanced head and neck cancer can be treated with either chemotherapy plus radiation, or with surgery followed by radiation. If surgery is the choice for treatment, it will be done to remove the cancer as well as some of the healthy tissue around it. Lymph nodes in the neck may also be removed. In certain cases, surgery may be followed by radiation treatment.

Despite initial treatment, in about three out of 10 patients with head and neck cancer the disease comes back (recurs) in the same location. In about 25 percent of patients, the disease eventually spreads to other organs. Patients are at higher risk for recurrence if their cancer has spread to lymph nodes or surrounding tissues in the neck and if the extent of the cancer is close to the edge of the tissue taken out during initial surgery. Five-year survival for patients with these risk factors is about 40 percent.

Previous studies have suggested that combining radiation therapy with chemotherapy (specifically, treatment with the drug cisplatin) is better for patients whose cancer is too large to have surgery and might improve outcomes for patients with head and neck cancer who have had surgery but are at high risk of experiencing a return of the disease. One of the effects of cisplatin is to increase the body's sensitivity to radiation.

The Studies

One of the current studies was conducted in Europe, the other in the United States.

The European study: The primary aim of this study was to find out if radiation plus chemotherapy (that is, combined therapy) would extend the time until the patients' disease progressed compared to radiation alone. A total of 334 patients were randomly assigned to receive either radiation alone or combined therapy after initial surgery. Patients were followed for a median of five years. The research team was led by Jacques Bernier, M.D., Ph.D., of the Oncology Institute of Southern Switzerland. (See the protocol summary ⁴.)

The U.S. study: The primary aim of this study was to find out if combined therapy would reduce the number of patients whose cancer came back in the same location. A total of 459 patients were randomly assigned to receive either radiation alone or combined therapy after initial surgery. The doses of radiation and chemotherapy were identical to those given in the European trial. Patients were followed for a median of just under four years. The research team was led by Jay S. Cooper, M.D., of New York University Medical Center. (See the protocol summary ⁵.)

Results

The European study: The researchers estimated that patients who received combined therapy lived for a median of 55 months before their disease progressed. By contrast, patients who received radiation alone lived for a median of 23 months before disease progression occurred.

An estimated 47 percent of patients treated with combined therapy survived for five years without progression of disease, compared with an estimated 36 percent of patients treated with radiation alone. Overall, an estimated 53 percent of patients in the combined-therapy group were still alive after five years, compared with an estimated 40 percent of patients in the radiation-alone group.

Patients treated with combined therapy had higher rates of side effects such as pain, loss of muscle flexibility, and difficulty swallowing. Patients treated with radiation alone had higher rates of mouth dryness. (See the journal abstract.)

The U.S. study: Forty-three patients were left out of the calculation of the study results after researchers determined they were ineligible for enrollment. Of the remaining 416 patients, 19 percent in the combined-therapy group had a recurrence of their cancer in the same location, compared with 30 percent in the radiation-alone group.

Survival free of disease was significantly longer for patients who received combined therapy. However, overall survival was about the same in the two groups. Severe side effects such as nausea, vomiting, and low white-blood-cell counts occurred in 77 percent of combined-therapy patients compared with 34 percent of radiation-alone patients. (See the journal abstract.)

Limitations

The median follow-up period in the U.S. study is less than four years, compared with five years in the European study, notes Barbara Conley, M.D., a medical oncologist with the Center for Cancer Research at the National Cancer Institute (NCI).

High rates of side effects to cisplatin meant that only about 50 percent of patients in the European study and 60 percent in the U.S. study completed the three prescribed courses of chemotherapy, Conley adds.

In an accompanying editorial, Michele I. Saunders, M.D., and Ana M. Rojas, M.D., of Mount Vernon Hospital in the United Kingdom say that despite the benefit conferred by combined therapy, about 30 percent of patients still had a recurrence of their cancer in the same location. Neither study found that combined therapy reduced the risk that a patient's cancer would spread to other organs, adds Conley.

Comments

“I think these results establish a new standard of care for adjuvant therapy [additional treatment following surgery] of patients with high-risk head and neck cancer,” says NCI’s Conley. She cautions, however, that combined therapy is not appropriate for all patients.

“Patients must be fit enough to undergo daily radiation treatment simultaneously with relatively high-dose cisplatin,” she says. “It will take a while to sort out which patients will benefit most from this approach, and research is needed to find treatments that will further improve survival.”

Glossary Terms

Treatment with drugs that kill cancer cells.

A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.

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

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

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.