TY - JOUR
T1 - A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma
AU - Evens, A. M.
AU - Carson, K. R.
AU - Kolesar, J.
AU - Nabhan, C.
AU - Helenowski, I.
AU - Islam, N.
AU - Jovanovic, B.
AU - Barr, P. M.
AU - Caimi, P. F.
AU - Gregory, S. A.
AU - Gordon, L. I.
N1 - Funding Information:
The work was presented in part at the American Society of Hematology (ASH), 54th Annual Meeting, Georgia, Atlanta, December 2012 and the 12th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 2013. The authors thank the University of Wisconsin Carbone Comprehensive Cancer Center (UWCCC) for use of its facilities to complete this research; the work was supported in part by NIH/NCI P30 CA014520 (UWCCC Support).
PY - 2013/12
Y1 - 2013/12
N2 - Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%. Patients and methods: We conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m2 twice/cycle) into the CODOXM/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function. Results: Among 25 BL patients, the median age was 44 years (23-70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40%of high-risk patients had bone marrow involvement, 35%had bulky disease and 15%had central nervous system involvement. The overall response rate was 100%(complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80%and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and diseasespecific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 μg/ml, respectively, versus 131 and 193 μg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 μg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively. Conclusions: The integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.
AB - Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%. Patients and methods: We conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m2 twice/cycle) into the CODOXM/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function. Results: Among 25 BL patients, the median age was 44 years (23-70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40%of high-risk patients had bone marrow involvement, 35%had bulky disease and 15%had central nervous system involvement. The overall response rate was 100%(complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80%and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and diseasespecific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 μg/ml, respectively, versus 131 and 193 μg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 μg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively. Conclusions: The integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.
KW - Burkitt's lymphoma
KW - Cancer
KW - Liposomal doxorubicin
KW - Non-Hodgkin's lymphoma
KW - Prognosis
KW - Rituximab
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U2 - 10.1093/annonc/mdt414
DO - 10.1093/annonc/mdt414
M3 - Article
C2 - 24146219
AN - SCOPUS:84888771030
SN - 0923-7534
VL - 24
SP - 3076
EP - 3081
JO - Annals of Oncology
JF - Annals of Oncology
IS - 12
ER -
