Two low-intensity chemotherapy regimens proved effective against Burkitt’s lymphoma and markedly less toxic than existing treatments, according to a report published online Nov. 13 in the New England Journal of Medicine.
In a prospective study, 30 consecutive patients with untreated Burkitt’s lymphoma were enrolled over a 10-year period in one of two low-intensity regimens; both included etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R). A complete remission was achieved in every patient and was sustained for a median of 73-86 months of follow-up, said Dr. Kieron M. Dunleavy of the National Cancer Institute and his associates.
"Low-intensity EPOCH-R–based therapy appears to obviate the need for high-intensity treatment and markedly reduces treatment toxicity while achieving high rates of durable response. Two confirmatory trials [of these regimens] are [now] under way in adults (NCT01092182) and children (NCT01760226)," they noted.
Until now, high-dose methotrexate and cytarabine were considered essential for control of this rare and typically aggressive cancer. "It is accepted that the high growth fraction and short doubling time of Burkitt’s lymphoma make intensive short-course chemotherapy a therapeutic necessity," albeit one that causes severe adverse effects and long-term morbidity. These study findings demonstrate that other less toxic approaches can be at least as effective, Dr. Dunleavy and his colleagues said.
The researchers undertook this study (NCT00001337 and NCT00006436) after hypothesizing that "the exquisite sensitivity of Burkitt’s lymphoma cells to genotoxic stress makes prolonged exposure time, not increased dose, the important therapeutic strategy for maximizing the killing of tumor cells." To test the idea, they studied 17 patients who had the sporadic variant of the malignancy and 13 who had the immunodeficiency-associated variant. Patients were aged 15-88 years, with a median age of 33.
Ten percent of the study population had high-risk disease, 17% had low-risk disease, and 73% had intermediate-risk disease.
The 19 patients who were HIV negative received a standard dose-adjusted EPOCH-R regimen. The 11 HIV-positive patients received a short-course regimen to reduce toxicity even further and got a double-dose of rituximab. The median cumulative dose of doxorubicin-etoposide was 47% lower and that of cyclophosphamide was 57% lower in the latter group.
All patients also were given filgrastim, beginning after the final dose of chemotherapy and continuing until absolute neutrophil recovery.
The HIV-negative group was followed for a median of 86 months and the HIV-positive group for a median of 73 months. At median follow-up, the HIV-negative group had a 95% rate of freedom from disease progression and an overall survival of 100%; the HIV-positive group had a 100% rate of freedom from disease progression and an overall survival of 90%.
Even though the latter group had more advanced Burkitt’s lymphoma as well as immunodeficiency, "they all had complete remissions that have been sustained without additional therapy," Dr. Dunleavy and his associates wrote (N. Engl. J. Med. 2013 Nov. 13 [doi:10.1056/NEJMoa1308392]).
At the most recent follow-up, none of the patients in either group had a disease recurrence or had died from Burkitt’s lymphoma. One HIV-positive patient died of acute myeloid leukemia nearly 3 years after completing the EPOCH-R regimen; it is not yet known whether the chemotherapy may have contributed to the later development of the leukemia, but HIV is a known risk factor for AML, the researchers noted.
There were no treatment-related deaths, and the toxic effects of both low-dose regimens were generally mild. Thrombocytopenia occurred in only 2% of the chemotherapy cycles; fever and neutropenia occurred in 22%. Almost all the chemotherapy infusions were outpatient, with hospital admission from fever and neutropenia occurring in 10% of cycles and only in HIV-positive patients.
This study was funded by the National Cancer Institute. Amgen provides filgrastim to NCI but had no other role in the study. No financial conflicts of interest were reported.