ASH: Chemotherapy Regimen Induces Complete Remissions in Burkitt's

ORLANDO, Dec. 11 -- A novel approach to Burkitt's lymphoma, using a regimen designed for large B-cell lymphomas, led to complete remissions in all patients in a small study, investigators reported here.

In a study of 19 patients with Burkitt's, the highly aggressive B-cell lymphoma, all 19 treated with dose-adjusted EPOCH with Rituxan (rituximab) had a complete remission, with few of the adverse events associated with standard chemotherapy for Burkitt's lymphoma, reported Kieron Dunleavy, M.D., of the National Cancer Institute in Bethesda, Md., colleagues.

Standard therapy for Burkitt's, a small, non-cleaved cell lymphoma, involves intensive high-dose chemotherapy with methotrexate, Ara-C (cytarabine), and other agents, noted Dr. Dunleavy at the American College of Hematology meeting.

Although this standard regimen induces complete remissions in more than 80% of patients, it's highly toxic and can be fatal in older patients and immuncompromised patients with HIV/AIDS, who have a 1,000-fold greater risk for developing Burkitt's lymphoma, said Dr. Dunleavy.

Treatment for Burkitt's is also commonly associated with tumor lysis syndrome, in which lysis of tumor cells causes rapid release of potassium, purine nucleic acids, and phosphorus into the bloodstream, which can in turn cause metabolic abnormalities that lead to acute renal failure.

Dose-adjusted EPOCH plus Rituxan (DA-EPOCH-R), developed at NCI, is a highly effective and well tolerated regimen used in the treatment of diffuse large B-cell lymphomas, the most common aggressive B-cell lymphoma. The regimen consists of dose-adjusted Vepesid (etoposide), prednisone, Oncovin (vincristine), Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Rituxan.

The investigators theorized that because it is given on an infusional schedule and targets rapidly dividing cells, and is dose-adjusted to the needs of individual patients, this regimen might also be effective in the treatment of patients with Burkitt's lymphoma.

Because younger patients tend to need much higher chemotherapy doses and more dose escalations than older patients, the dose-adjustment aspect of the EPOCH-R regimen could be beneficial for Burkitt's lymphoma, which tends to strike younger patients.

They studied the regimen in 19 patients, median age 29, with newly diagnosed Burkitt's, 53% with advanced stage disease (III or IV). Sixty-five patients had extranodal disease with abdominal or pelvic involvement at diagnosis.

Eligible patients had untreated Burkitt's lymphoma, and could be HIV positive or negative. HIV negative patients received six cycles of DA-EPOCH-R. Patients with HIV-associated Burkitt's received three-to-six cycles of DA-EPOCH-R for one cycle beyond complete remission for a minimum of three cycles.

All patients received intrathecal methotrexate prophylaxis, and therapy was administered in the outpatient clinic where possible.

The investigators found that the regimen induced remission in 100% of patients, and that all patients remained in remission at an average follow-up of 28 months.

The treatment was also well tolerated, with patients hospitalized for low blood counts and fever after only 16% of chemotherapy cycles, and tumor lysis syndrome occurring in only one patient out of 19.

The investigators concluded that the DA-EPOCH-R is highly effective with relatively low toxicity compared to standard intensive high-dose regimens for Burkitt's lymphoma, and that infusional chemotherapy may reduce the risk of tumor lysis syndrome.

The study, which is continuing to accrue patients, was funded by the National Cancer Institute. Neither Dr. Dunleavy nor his colleagues had any financial conflicts of interest.