Lower-Toxicity Treatment Effective in Some Cases of Early-Stage Hodgkin's LymphomaKey Words
Hodgkin’s lymphoma, involved-field radiation therapy, multidrug chemotherapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
An experimental low-intensity four-drug chemotherapy regimen plus limited radiation therapy improved cancer-free survival in patients with early-stage Hodgkin’s lymphoma who had a favorable outlook. However, patients with an unfavorable outlook did better with standard six-drug chemotherapy plus limited radiation therapy.
Source
Journal of Clinical Oncology, published online, June 5, 2006; in print July 1, 2006 (see the journal abstract).
(J Clin Oncol. 2006 Jul 1;24(19):3128-35. Epub 2006 Jun 5)
Background
Hodgkin’s lymphoma is a rare cancer of the lymphatic system – the tissues and organs that produce, store, and carry white blood cells. Advances in treatment have improved the outlook for patients with Hodgkin’s lymphoma, particularly if the disease is caught early. Eighty-five percent of patients diagnosed with Hodgkin’s lymphoma are alive five years later.
However, treatment with radiation and multidrug chemotherapy can lead to severe long-term adverse effects, including heart and lung problems, sterility, and second cancers. Researchers are studying how to refine chemotherapy and radiation treatment regimens to give patients the best chance of long-term survival while lowering the risk of severe long-term side-effects.
The Study
Researchers in Europe designed this study with the aim of reducing the long-term side effects of treatment – in particular, the occurrence of second cancers - as much as possible. Between 1988 and 1993, they recruited 722 patients in eight countries. All of the patients had stage I or stage II Hodgkin’s lymphoma.
The patients were divided into two groups on the basis of factors that previous studies had shown can predict a favorable or unfavorable outlook. Patients in the favorable-outlook group were assigned at random to one of the two following treatments.
- Radiation therapy to the neck and chest and to the lymph nodes under the arms, in the upper abdomen, and in the pelvis
- An experimental “low intensity” four-drug chemotherapy regimen consisting of epirubicin, bleomycin, vinblastine, and prednisone (EBVP), followed by radiation therapy only to the areas of the body where disease was present (known as involved-field radiation therapy)
By limiting radiation therapy to the diseased areas, other healthy organs such as the heart and lungs are better protected from radiation’s toxic effects. Previous studies have shown that focused approaches such as involved-field radiation therapy pose a lower risk of causing second cancers later on.
Patients in the unfavorable-outlook group were assigned at random to one of the two following treatments.
- A standard six-drug chemotherapy regimen consisting of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) plus involved-field radiation therapy
- The experimental low-intensity EBVP regimen plus involved-field radiation therapy
Researchers followed the patients for a median of nine years.
The principal investigator for the study was Evert M. Noordijk, M.D., of Leiden University Medical Center in Leiden, the Netherlands.
Results
Among the favorable-outlook patients, 88 percent of those treated with EBVP plus involved-field radiation therapy were alive, had not had a recurrence of Hodgkin’s lymphoma, and had not developed a second cancer, compared with 78 percent of those who received extensive radiation treatment only. Three out of 168 patients (1.8 percent) in the EBVP group got a second cancer, compared with six out of 165 patients (3.6 percent) who were treated with extensive radiation.
Overall survival was identical (92 percent) for both groups of favorable-outlook patients.
Among the patients with an unfavorable outlook, 88 percent of those treated with MOPP/ABV plus involved-field radiation treatment were alive, had not had a recurrence of Hodgkin’s lymphoma, and had not developed a second cancer, compared with 68 percent of those who received the experimental EBVP regimen plus radiation. Eight out of 195 patients (4.1 percent) in the MOPP/ABV group got a second cancer, compared with 16 out of 194 (8.2 percent) in the EBVP group.
Overall survival was 88 percent for patients in the MOPP/ABV group and 79 percent in the EBVP group.
Limitations
Doctors in the United States are less likely than those in Europe to use the drug epirubicin, one component of this study’s experimental EBVP regimen, to treat patients with Hodgkin’s lymphoma, says Michael Bishop, M.D., of the National Cancer Institute’s Center for Cancer Research.
Standard practice in the U.S. is to use doxorubicin (a drug in the same class as epirubicin) together with bleomycin, vincristine, and dacarbazine (a drug in the same class as prednisone) - a combination known as ABVD. The difference between ABVD and EBVP is comparable to “the difference between two kinds of oranges,” says Bishop.
Comments
In the past, radiation therapy was considered the best treatment for early-stage Hodgkin’s lymphoma and chemotherapy was considered too toxic, the study authors write. In recent years, however, they say “treatment strategies have changed dramatically. Now, all Hodgkin’s patients, even with limited disease, will receive primarily chemotherapy” with radiation to diseased areas only.
This study’s most important finding is that the standard chemotherapy regimen of MOPP/ABV was more effective than the experimental EBVP drug combination in patients with an unfavorable outlook, comments Bishop.
“Standard chemotherapy plus involved-field radiation therapy remains the best option” for Hodgkin’s lymphoma patients with an unfavorable outlook, he says.
For patients with a favorable outlook, this study’s findings suggest that doctors could consider combining a chemotherapy regimen such as ABVD with involved-field radiation therapy to reduce the likelihood of second cancers, Bishop adds.
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