Less-Intense Chemotherapy Benefits Some Children With B-Cell Non-Hodgkin Lymphoma
B-cell non-Hodgkin lymphoma, childhood cancers. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Children and adolescents with less advanced B-cell non-Hodgkin lymphoma did just as well, and suffered fewer side effects, when treated with lower doses of multidrug chemotherapy than is called for by the current standard of care. For young people whose disease was more advanced, however, lower doses of chemotherapy caused fewer side effects but were slightly less likely to prevent the cancer from coming back.
Non-Hodgkin lymphoma (NHL) is a rare cancer in children; about 800 new cases are diagnosed each year in the United States. B-cell lymphoma is a type of NHL that occurs in the B cells, white blood cells whose normal job is to protect the body from infection by bacteria and viruses.
NHL is usually treated with multidrug chemotherapy. Surgery is not often done because it is unlikely to cure the disease and may damage normal organs. With current treatments, about 80 percent of children and adolescents with NHL survive for at least five years. When the disease is confined to one part of the body (for example, the neck, groin, or underarm, but not the chest or abdomen), about 90 percent of patients survive for at least five years.
In a large clinical trial published in 2001, researchers found that children with less advanced B-cell lymphoma could be successfully treated with lower doses of chemotherapy drugs than children with more advanced disease. The multidrug regimens used in that study, known as LMB-89, became standard therapy for B-cell lymphoma in children. However, most patients treated with these regimens suffer moderate to severe side effects such as infection and mouth sores. In addition, the regimen includes high doses of cyclophosphamide, a drug that can cause infertility.
An international group of researchers (from the United States, the United Kingdom, and France) wanted to find out whether further reducing chemotherapy doses would be equally effective while producing fewer side effects. Between 1996 and 2001, they conducted a large clinical trial that included children and adolescents with less-advanced, intermediate-risk B-cell lymphoma, as well as children and adolescents with advanced, high-risk disease. Separate treatment regimens were used for these two patient groups and separate questions of therapy were evaluated for each group.
This component of the study involved 657 patients ranging in age from two to 20. The patients’ cancers ranged from stage I to stage IV disease with only limited spread to the bone marrow (less than 25 percent involvement) and without spread to the brain or spinal fluid.
Patients were randomly assigned to four treatment regimens to address two questions of therapy: The first question was whether a course of maintenance therapy was necessary after four courses of intensive chemotherapy. The second question addressed whether reduced-intensity drug therapy that included half the standard dose of cyclophosphamide was as effective as standard-intensity drug therapy.
The principal investigator for this part of the study was Catherine Patte, M.D., of the Institut Gustave Roussy in Villejuif, France.
Results for Intermediate-Risk Patients
After a median follow-up period of 4.5 years, rates of both overall survival and progression-free survival were similar for patients who received lower doses of cyclophosphamide compared to those who received full doses of cyclophosphamide.
Survival and progression-free survival rates were also similar for patients who received no maintenance course compared to those who got the maintenance course. Patients who received reduced treatment experienced fewer side effects than did patients who received full doses of cyclophosphamide and/or maintenance therapy.
This component of the study involved 190 patients ranging in age from under a year to 19 years. All had stage IV B-cell lymphoma that had spread to the bone marrow, the brain or spinal fluid, or both.
Patients were randomly assigned to one of two treatment groups.
- Group 1 standard multidrug chemotherapy, including full doses of the drugs cytarabine and etoposide, plus four courses of maintenance therapy.
- Group 2 received reduced-intensity therapy, including lower doses of cytarabine and etoposide, and only one maintenance course.
The principal investigator for this part of the study was Mitchell Cairo, M.D., of Morgan Stanley Children’s Hospital in New York.
Results for High-Risk Patients
Patients who received reduced-intensity therapy suffered fewer side effects such as infections, mouth ulcers, and hospitalizations, compared with those who got standard therapy. After four years, however, more patients who received standard therapy (90 percent) remained cancer-free, compared with those who received reduced-intensity therapy (80 percent).
“From these studies, we can…conclude that a modest reduction in intensity of therapy is probably safe for children with a better [outlook], and a slightly less modest reduction for those with a worse [outlook] is very likely…to result in a worse outcome,” writes Adele K. Fielding, M.D., of the Royal Free and University College Medical School in London, United Kingdom, in an accompanying editorial.
The results establish a new standard of care for children with intermediate-risk B-cell NHL that reduces both short-term and long-term side effects of therapy while maintaining very favorable outcome, says Malcolm Smith, M.D., Ph.D., a pediatric cancer specialist with the National Cancer Institute's Cancer Therapy Evaluation Program.
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