Low-intensity therapy in adults with Burkitt's lymphoma

Abstract

Background: Burkitt's lymphoma is an aggressive B-cell lymphoma that occurs in children and adults and is largely curable with the use of intensive and toxic chemotherapy. Current treatments are less effective and have more severe side effects in adults and patients with immunodeficiency than in children.

Methods: We studied low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) in patients with untreated Burkitt's lymphoma. Two EPOCH-R regimens were tested: a standard dose-adjusted combination in human immunodeficiency virus (HIV)-negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group).

Results: A total of 30 consecutive patients were treated; 19 patients were in the DA-EPOCH-R group, and 11 in the SC-EPOCH-RR group. The overall median age of the patients was 33 years, and 40% were 40 years of age or older; 73% of the patients had intermediate-risk disease, and 10% had high-risk disease. The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin-etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt's lymphoma.

Conclusions: In this uncontrolled prospective study, low-intensity EPOCH-R-based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt's lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov numbers, NCT00001337 and NCT00006436.).

Figure 1. Kaplan–Meier Estimates of Freedom from Disease Progression and Overall Survival

Panels A and B show the estimates of freedom from progression of disease and overall survival, respectively, among patients who received a dose-adjusted combination of etoposide, doxorubicin, and vincristine with cyclophosphamide, prednisone, and rituximab (DA-EPOCH-R). Panels C and D show the estimates of freedom from progression and overall survival, respectively, among patients who received a short course of the combination therapy with a double dose of rituximab in each cycle (SC-EPOCH-RR). Panels E and F show the estimates of freedom from progression and overall survival, respectively, among patients who had the immunodeficiency-associated variant of Burkitt’s lymphoma.

Figure 2. Cumulative Drug Doses and Infusional and Bolus Administrations of Doxorubicin

The median cumulative doses of doxorubicin–etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group (Panel A). In a comparison of the maximal exposure of doxorubicin when administered at dose levels 1 and 3 in the DA-EPOCH-R group (see the Supplementary Appendix), we found a significant difference of 45% in the area under the concentration–time curves (1140 ng per milliliter per hour and 1650 ng per milliliter per hour, respectively) (Panel B). Purple symbols indicate drug concentrations at dose level 1, and yellow symbols drug concentrations at dose level 3. Circles indicate Patient 1, who only had a measurement for dose level 3 at 96 hours but had measurements for both dose levels at 24 hours; diamonds and squares, respectively, indicate Patients 2 and 3, who had measurements for both dose levels at 24 and 96 hours. In a simulation of a 0.5-hour bolus-administration schedule, bolus administration led to transient high peak concentrations (Panel C).