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Key words
low-grade non-Hodgkin lymphoma, chemotherapy, radiation therapy, watchful waiting. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary
Patients with advanced low-grade (slow-growing) non-Hodgkin’s lymphoma who have no symptoms can safely delay chemotherapy until symptoms develop, according to a British study.

Source
The Lancet, August 16, 2003 (see the journal abstract).

Background
Low-grade non-Hodgkin’s lymphoma is usually a slow-growing cancer. Even at advanced stages the disease may have no symptoms. It is a challenging disease to treat because although chemotherapy, biologicals (e.g., vaccines), and radiation therapy are all effective at shrinking the disease, the disease is not curable.

Because of the disease’s slow-growing nature, patients may live for several years without any treatment. This has led some researchers to question the need for immediate treatment of patients with this disease in the absence of troublesome symptoms.

The Study
This study was designed to determine whether patients with advanced but symptom-free, low-grade non-Hodgkin’s lymphoma who received immediate chemotherapy survived any longer than patients whose chemotherapy was delayed until their disease worsened and symptoms appeared. The latter approach is known as observation or “watchful waiting.”

Between 1981 and 1990, 309 patients at 44 centers across the United Kingdom were randomly assigned to receive either immediate chemotherapy with the drug chlorambucil or watchful waiting. Those assigned to watchful waiting were evaluated by their doctors at least once every three months. If their disease worsened, they began treatment with the same chemotherapy regimen given to patients in the other group.

Half of the patients were aged 60 or under when they enrolled in the study. About 35 percent were aged 61 to 70 and 15 percent were over 70. All patients were followed up for a median of 16 years.

The study was led by Kirit Ardeshna from the Mount Vernon Cancer Centre, Northwood, United Kingdom.

Results
Median survival among patients in the group that received immediate chemotherapy was 5.9 years, compared with 6.7 years for patients in the watchful waiting group. This difference was not statistically significant — that is, it could have occurred by chance.

Roughly 40 percent of all deaths among study participants were due to causes other than non-Hodgkin’s lymphoma. Among patients who died of non-Hodgkin’s lymphoma, median survival was almost identical whether they were assigned to immediate chemotherapy or to watchful waiting.

About three-quarters of the patients assigned to watchful waiting later received chemotherapy because their disease progressed. The median time until these patients needed chemotherapy was about two and a half years. Overall, patients in the watchful waiting group had about a 20 percent chance of not requiring chemotherapy after 10 years. However, for patients over age 70, the chance of not needing chemotherapy after 10 years was doubled to 40 percent.

“This study confirms that early intervention in asymptomatic [symptom-free] patients does not prolong survival and that ‘watch and wait’ is a valid approach,” said Wyndham Wilson, M.D., Ph.D., of the National Cancer Institute’s Center for Clinical Research. “In particular, waiting makes sense for patients over age 70.”

Limitations
The study compares watchful waiting to chemotherapy with a relatively old drug, chlorambucil. It does not address whether early treatment with newer experimental approaches, such as vaccines and monoclonal antibodies, would prolong patients’ survival, said Wilson.

Glossary Terms

Pertaining to biology or to life and living things. In medicine, refers to a substance made from a living organism or its products. Biologicals may be used to prevent, diagnose, treat or relieve of symptoms of a disease. For example, antibodies, interleukins, and vaccines are biologicals. Biological also refers to parents and children who are related by blood.

Treatment with drugs that kill cancer cells.

An anticancer drug that belongs to the family of drugs called alkylating agents.

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 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.

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

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called active surveillance, expectant management, and observation.