Patients with a type of cancer known as primary mediastinal B-cell lymphoma who received infusions of chemotherapy, but who did not have radiation therapy to an area of the thorax known as the mediastinum, had excellent outcomes, according to clinical trial results. Until now, most standard treatment approaches for patients with this type of lymphoma have included radiation therapy to the mediastinum. However, mediastinal radiation is associated with substantial long-term toxic side effects.
The results of this single arm trial, which followed 51 patients for a period of up to 14 years, was conducted by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and appeared April 11, 2013, in The New England Journal of Medicine.
Primary mediastinal B-cell lymphoma mainly affects people from their teenage years to their early 30s. Many patients are cured with a combination of chemotherapy and radiation therapy. However, even with this treatment, about 20 percent of patients see their disease progress.
Most patients receive radiation to the chest area, which can cause new cancers as well as damage to the heart. This is particularly a problem for young people because the risk of new cancers and heart disease continues to increase as they get older. Primary mediastinal B-cell lymphoma is also more common in women, who are at greater risk of developing breast cancer from radiation therapy to the chest.
Two NCI investigators reviewing CT scan on computer screen with 26 year old male patient, shown at far right. Cross-sectional scan on right side of screen shows 15 cm tumor mass in mediastinum and scan on left shows complete remission 7 months later with no tumor evident.
Wyndham Wilson, M.D., Ph.D., head of NCI's Lymphoma Therapeutics Section, and colleagues conducted the trial, in which every patient received the drugs etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab in a regimen known as dose-adjusted EPOCH-R, or DA-EPOCH-R. This regimen uses infusion strategies in which doses of the drugs etoposide, doxorubicin, and cyclophosphamide are adjusted for greatest efficacy.
Fifty-one patients with untreated primary mediastinal B-cell lymphoma were included in this phase II study. The maximum tumor diameter was 11 centimeters. All but two patients achieved a complete remission with DA-EPOCH-R therapy, and none of the patients with a complete remission have developed a recurrent lymphoma. The two patients who did not achieve a complete remission received radiation and have also not had their tumors recur. There was no evidence of other diseases developing later on or cardiac toxic effects.
"The high success of this regimen in greatly reducing the need for radiation and improving the cure rate in this disease may relate to specialized dosing and continuous infusion delivery of the EPOCH-R agents," said Wilson.
To provide an independent assessment of their DA-EPOCH-R trial results, the researchers collaborated with investigators at Stanford University (Calif.) Medical Center, who had used this regimen to treat 16 patients with primary mediastinal B-cell lymphoma. The patients were similar to those treated in the NCI study except for being slightly older and having a lower frequency of disease outside the mediastinum. All 16 Stanford patients who received this regimen are also in remission and none required radiation treatment.
Studies have suggested that primary mediastinal B-cell lymphoma has a better outcome with more dose-intense regimens. Other studies have also demonstrated that the use of rituximab in the drug regimen may improve treatment, hence the use of DA-EPOCH-R as opposed to just EPOCH.
"For me, these results are exciting and demonstrate that, using this approach, almost all patients appear to be cured and very few patients require radiation," said Kieron Dunleavy, M.D., NCI, and first author on the study. "Based on our results, an international phase II trial of DA-EPOCH-R in pediatric patients with primary mediastinal B-cell lymphoma is ongoing to confirm these findings, and we hope this international trial will have a similarly positive outcome."
The trial is registered at www.clinicaltrials.gov as NCT00001337.
- Kieron Dunleavy, Stefania Pittaluga, Lauren S. Maeda, Ranjana Advani, Clara C. Chen, Julie Hessler, Seth M. Steinberg, Cliona Grant, George Wright, Gaurav Varma, Louis M. Staudt, Elaine S. Jaffe, Wyndham H. Wilson. Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma. New England Journal of Medicine, 2013; 368 (15): 1408 DOI: 10.1056/NEJMoa1214561
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